ERX4412543 E-MTAB-94021598011819:4598STDY7805100_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960968 SAMEA7200749 4598STDY7805100_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412544 E-MTAB-94021598011819:4598STDY7805101_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960969 SAMEA7200750 4598STDY7805101_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412545 E-MTAB-94021598011819:4598STDY7805102_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960970 SAMEA7200751 4598STDY7805102_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412546 E-MTAB-94021598011819:4598STDY7805103_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960971 SAMEA7200752 4598STDY7805103_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412547 E-MTAB-94021598011819:4598STDY7805104_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960972 SAMEA7200753 4598STDY7805104_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412548 E-MTAB-94021598011819:4598STDY7805105_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960973 SAMEA7200754 4598STDY7805105_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412549 E-MTAB-94021598011819:4598STDY7805106_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960974 SAMEA7200755 4598STDY7805106_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412550 E-MTAB-94021598011819:4598STDY7805107_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960975 SAMEA7200756 4598STDY7805107_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412551 E-MTAB-94021598011819:4598STDY7805108_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960976 SAMEA7200757 4598STDY7805108_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412552 E-MTAB-94021598011819:4598STDY7805109_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960977 SAMEA7200758 4598STDY7805109_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412553 E-MTAB-94021598011819:4598STDY7805110_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960978 SAMEA7200759 4598STDY7805110_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412554 E-MTAB-94021598011819:4598STDY7805111_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960979 SAMEA7200760 4598STDY7805111_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412555 E-MTAB-94021598011819:4598STDY7805112_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960980 SAMEA7200761 4598STDY7805112_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412556 E-MTAB-94021598011819:4598STDY7805113_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960981 SAMEA7200762 4598STDY7805113_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412557 E-MTAB-94021598011819:4598STDY7805114_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960982 SAMEA7200763 4598STDY7805114_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412558 E-MTAB-94021598011819:4598STDY7805115_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960983 SAMEA7200764 4598STDY7805115_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412559 E-MTAB-94021598011819:4598STDY7805116_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960984 SAMEA7200765 4598STDY7805116_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412560 E-MTAB-94021598011819:4598STDY7805117_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960985 SAMEA7200766 4598STDY7805117_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412561 E-MTAB-94021598011819:4598STDY7805118_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960986 SAMEA7200767 4598STDY7805118_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412562 E-MTAB-94021598011819:4598STDY7805119_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960987 SAMEA7200768 4598STDY7805119_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412563 E-MTAB-94021598011819:4598STDY7805120_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960988 SAMEA7200769 4598STDY7805120_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412564 E-MTAB-94021598011819:4598STDY7805121_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960989 SAMEA7200770 4598STDY7805121_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412565 E-MTAB-94021598011819:4598STDY7805122_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960990 SAMEA7200771 4598STDY7805122_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412566 E-MTAB-94021598011819:4598STDY7805123_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960991 SAMEA7200772 4598STDY7805123_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412567 E-MTAB-94021598011819:4598STDY7805124_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960992 SAMEA7200773 4598STDY7805124_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412568 E-MTAB-94021598011819:4598STDY7805125_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960993 SAMEA7200774 4598STDY7805125_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412569 E-MTAB-94021598011819:4598STDY7805126_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960994 SAMEA7200775 4598STDY7805126_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412570 E-MTAB-94021598011819:4598STDY7805127_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960995 SAMEA7200776 4598STDY7805127_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412571 E-MTAB-94021598011819:4598STDY7805128_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960996 SAMEA7200777 4598STDY7805128_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412572 E-MTAB-94021598011819:4598STDY7805129_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960997 SAMEA7200778 4598STDY7805129_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412573 E-MTAB-94021598011819:4598STDY7805130_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960998 SAMEA7200779 4598STDY7805130_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412574 E-MTAB-94021598011819:4598STDY7805131_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4960999 SAMEA7200780 4598STDY7805131_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412575 E-MTAB-94021598011819:4598STDY7805132_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961000 SAMEA7200781 4598STDY7805132_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412576 E-MTAB-94021598011819:4598STDY7805133_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961001 SAMEA7200782 4598STDY7805133_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412577 E-MTAB-94021598011819:4598STDY7805134_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961002 SAMEA7200783 4598STDY7805134_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412578 E-MTAB-94021598011819:4598STDY7805135_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961003 SAMEA7200784 4598STDY7805135_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412579 E-MTAB-94021598011819:4598STDY7805136_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961004 SAMEA7200785 4598STDY7805136_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412580 E-MTAB-94021598011819:4598STDY7805137_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961005 SAMEA7200786 4598STDY7805137_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412581 E-MTAB-94021598011819:4598STDY7805138_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961006 SAMEA7200787 4598STDY7805138_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412582 E-MTAB-94021598011819:4598STDY7805139_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961007 SAMEA7200788 4598STDY7805139_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412583 E-MTAB-94021598011819:4598STDY7805140_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961008 SAMEA7200789 4598STDY7805140_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412584 E-MTAB-94021598011819:4598STDY7805141_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961009 SAMEA7200790 4598STDY7805141_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412585 E-MTAB-94021598011819:4598STDY7805142_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961010 SAMEA7200791 4598STDY7805142_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412586 E-MTAB-94021598011819:4598STDY7805143_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961011 SAMEA7200792 4598STDY7805143_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412587 E-MTAB-94021598011819:4598STDY7805144_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961012 SAMEA7200793 4598STDY7805144_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412588 E-MTAB-94021598011819:4598STDY7805145_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961013 SAMEA7200794 4598STDY7805145_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412589 E-MTAB-94021598011819:4598STDY7805146_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961014 SAMEA7200795 4598STDY7805146_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412590 E-MTAB-94021598011819:4598STDY7805147_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961015 SAMEA7200796 4598STDY7805147_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412591 E-MTAB-94021598011819:4598STDY7805148_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961016 SAMEA7200797 4598STDY7805148_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412592 E-MTAB-94021598011819:4598STDY7805149_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961017 SAMEA7200798 4598STDY7805149_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412593 E-MTAB-94021598011819:4598STDY7805150_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961018 SAMEA7200799 4598STDY7805150_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412594 E-MTAB-94021598011819:4598STDY7805151_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961019 SAMEA7200800 4598STDY7805151_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412595 E-MTAB-94021598011819:4598STDY7805152_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961020 SAMEA7200801 4598STDY7805152_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412596 E-MTAB-94021598011819:4598STDY7805153_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961021 SAMEA7200802 4598STDY7805153_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412597 E-MTAB-94021598011819:4598STDY7805154_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961022 SAMEA7200803 4598STDY7805154_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412598 E-MTAB-94021598011819:4598STDY7805155_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961023 SAMEA7200804 4598STDY7805155_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412599 E-MTAB-94021598011819:4598STDY7805156_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961024 SAMEA7200805 4598STDY7805156_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412600 E-MTAB-94021598011819:4598STDY7805157_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961025 SAMEA7200806 4598STDY7805157_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412601 E-MTAB-94021598011819:4598STDY7805158_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961026 SAMEA7200807 4598STDY7805158_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412602 E-MTAB-94021598011819:4598STDY7805159_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961027 SAMEA7200808 4598STDY7805159_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412603 E-MTAB-94021598011819:4598STDY7805160_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961028 SAMEA7200809 4598STDY7805160_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412604 E-MTAB-94021598011819:4598STDY7805161_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961029 SAMEA7200810 4598STDY7805161_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412605 E-MTAB-94021598011819:4598STDY7805162_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961030 SAMEA7200811 4598STDY7805162_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412606 E-MTAB-94021598011819:4598STDY7805163_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961031 SAMEA7200812 4598STDY7805163_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412607 E-MTAB-94021598011819:4598STDY7805164_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961032 SAMEA7200813 4598STDY7805164_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412608 E-MTAB-94021598011819:4598STDY7805165_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961033 SAMEA7200814 4598STDY7805165_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412609 E-MTAB-94021598011819:4598STDY7805166_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961034 SAMEA7200815 4598STDY7805166_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412610 E-MTAB-94021598011819:4598STDY7805167_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961035 SAMEA7200816 4598STDY7805167_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412611 E-MTAB-94021598011819:4598STDY7805168_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961036 SAMEA7200817 4598STDY7805168_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412612 E-MTAB-94021598011819:4598STDY7805169_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961037 SAMEA7200818 4598STDY7805169_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412613 E-MTAB-94021598011819:4598STDY7805170_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961038 SAMEA7200819 4598STDY7805170_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412614 E-MTAB-94021598011819:4598STDY7805171_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961039 SAMEA7200820 4598STDY7805171_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412615 E-MTAB-94021598011819:4598STDY7805172_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961040 SAMEA7200821 4598STDY7805172_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412616 E-MTAB-94021598011819:4598STDY7805173_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961041 SAMEA7200822 4598STDY7805173_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412617 E-MTAB-94021598011819:4598STDY7805174_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961042 SAMEA7200823 4598STDY7805174_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412618 E-MTAB-94021598011819:4598STDY7805175_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961043 SAMEA7200824 4598STDY7805175_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412619 E-MTAB-94021598011819:4598STDY7805176_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961044 SAMEA7200825 4598STDY7805176_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412620 E-MTAB-94021598011819:4598STDY7805177_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961045 SAMEA7200826 4598STDY7805177_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412621 E-MTAB-94021598011819:4598STDY7805178_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961046 SAMEA7200827 4598STDY7805178_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412622 E-MTAB-94021598011819:4598STDY7805179_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961047 SAMEA7200828 4598STDY7805179_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412623 E-MTAB-94021598011819:4598STDY7805180_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961048 SAMEA7200829 4598STDY7805180_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412624 E-MTAB-94021598011819:4598STDY7805181_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961049 SAMEA7200830 4598STDY7805181_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412625 E-MTAB-94021598011819:4598STDY7805182_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961050 SAMEA7200831 4598STDY7805182_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412626 E-MTAB-94021598011819:4598STDY7805183_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961051 SAMEA7200832 4598STDY7805183_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412627 E-MTAB-94021598011819:4598STDY7805184_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961052 SAMEA7200833 4598STDY7805184_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412628 E-MTAB-94021598011819:4598STDY7805185_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961053 SAMEA7200834 4598STDY7805185_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412629 E-MTAB-94021598011819:4598STDY7805186_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961054 SAMEA7200835 4598STDY7805186_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412630 E-MTAB-94021598011819:4598STDY7805187_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961055 SAMEA7200836 4598STDY7805187_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412631 E-MTAB-94021598011819:4598STDY7805188_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961056 SAMEA7200837 4598STDY7805188_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412632 E-MTAB-94021598011819:4598STDY7805189_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961057 SAMEA7200838 4598STDY7805189_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412633 E-MTAB-94021598011819:4598STDY7805190_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961058 SAMEA7200839 4598STDY7805190_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412634 E-MTAB-94021598011819:4598STDY7805191_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961059 SAMEA7200840 4598STDY7805191_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412635 E-MTAB-94021598011819:4598STDY7805192_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961060 SAMEA7200841 4598STDY7805192_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412636 E-MTAB-94021598011819:4598STDY7805193_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961061 SAMEA7200842 4598STDY7805193_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412637 E-MTAB-94021598011819:4598STDY7805194_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961062 SAMEA7200843 4598STDY7805194_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412638 E-MTAB-94021598011819:4598STDY7805195_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961063 SAMEA7200844 4598STDY7805195_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412639 E-MTAB-94021598011819:4598STDY7805196_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961064 SAMEA7200845 4598STDY7805196_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412640 E-MTAB-94021598011819:4598STDY7805197_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961065 SAMEA7200846 4598STDY7805197_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412641 E-MTAB-94021598011819:4598STDY7805198_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961066 SAMEA7200847 4598STDY7805198_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412642 E-MTAB-94021598011819:4598STDY7805199_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961067 SAMEA7200848 4598STDY7805199_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412643 E-MTAB-94021598011819:4598STDY7805200_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961068 SAMEA7200849 4598STDY7805200_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412644 E-MTAB-94021598011819:4598STDY7805201_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961069 SAMEA7200850 4598STDY7805201_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412645 E-MTAB-94021598011819:4598STDY7805202_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961070 SAMEA7200851 4598STDY7805202_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412646 E-MTAB-94021598011819:4598STDY7805203_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961071 SAMEA7200852 4598STDY7805203_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412647 E-MTAB-94021598011819:4598STDY7805204_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961072 SAMEA7200853 4598STDY7805204_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412648 E-MTAB-94021598011819:4598STDY7805205_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961073 SAMEA7200854 4598STDY7805205_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412649 E-MTAB-94021598011819:4598STDY7805206_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961074 SAMEA7200855 4598STDY7805206_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412650 E-MTAB-94021598011819:4598STDY7805207_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961075 SAMEA7200856 4598STDY7805207_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412651 E-MTAB-94021598011819:4598STDY7805208_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961076 SAMEA7200857 4598STDY7805208_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412652 E-MTAB-94021598011819:4598STDY7805209_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961077 SAMEA7200858 4598STDY7805209_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412653 E-MTAB-94021598011819:4598STDY7805210_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961078 SAMEA7200859 4598STDY7805210_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412654 E-MTAB-94021598011819:4598STDY7805211_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961079 SAMEA7200860 4598STDY7805211_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412655 E-MTAB-94021598011819:4598STDY7805212_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961080 SAMEA7200861 4598STDY7805212_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412656 E-MTAB-94021598011819:4598STDY7805213_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961081 SAMEA7200862 4598STDY7805213_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412657 E-MTAB-94021598011819:4598STDY7805214_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961082 SAMEA7200863 4598STDY7805214_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412658 E-MTAB-94021598011819:4598STDY7805215_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961083 SAMEA7200864 4598STDY7805215_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412659 E-MTAB-94021598011819:4598STDY7805216_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961084 SAMEA7200865 4598STDY7805216_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412660 E-MTAB-94021598011819:4598STDY7805217_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961085 SAMEA7200866 4598STDY7805217_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412661 E-MTAB-94021598011819:4598STDY7805218_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961086 SAMEA7200867 4598STDY7805218_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412662 E-MTAB-94021598011819:4598STDY7805219_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961087 SAMEA7200868 4598STDY7805219_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412663 E-MTAB-94021598011819:4598STDY7805220_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961088 SAMEA7200869 4598STDY7805220_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412664 E-MTAB-94021598011819:4598STDY7805221_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961089 SAMEA7200870 4598STDY7805221_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412665 E-MTAB-94021598011819:4598STDY7805222_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961090 SAMEA7200871 4598STDY7805222_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412666 E-MTAB-94021598011819:4598STDY7805223_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961091 SAMEA7200872 4598STDY7805223_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412667 E-MTAB-94021598011819:4598STDY7805224_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961092 SAMEA7200873 4598STDY7805224_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412668 E-MTAB-94021598011819:4598STDY7805225_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961093 SAMEA7200874 4598STDY7805225_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412669 E-MTAB-94021598011819:4598STDY7805226_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961094 SAMEA7200875 4598STDY7805226_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412670 E-MTAB-94021598011819:4598STDY7805227_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961095 SAMEA7200876 4598STDY7805227_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412671 E-MTAB-94021598011819:4598STDY7805228_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961096 SAMEA7200877 4598STDY7805228_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412672 E-MTAB-94021598011819:4598STDY7805229_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961097 SAMEA7200878 4598STDY7805229_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412673 E-MTAB-94021598011819:4598STDY7805230_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961098 SAMEA7200879 4598STDY7805230_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412674 E-MTAB-94021598011819:4598STDY7805231_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961099 SAMEA7200880 4598STDY7805231_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412675 E-MTAB-94021598011819:4598STDY7805232_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961100 SAMEA7200881 4598STDY7805232_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412676 E-MTAB-94021598011819:4598STDY7805233_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961101 SAMEA7200882 4598STDY7805233_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412677 E-MTAB-94021598011819:4598STDY7805234_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961102 SAMEA7200883 4598STDY7805234_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412678 E-MTAB-94021598011819:4598STDY7805235_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961103 SAMEA7200884 4598STDY7805235_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412679 E-MTAB-94021598011819:4598STDY7805236_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961104 SAMEA7200885 4598STDY7805236_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412680 E-MTAB-94021598011819:4598STDY7805237_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961105 SAMEA7200886 4598STDY7805237_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412681 E-MTAB-94021598011819:4598STDY7805238_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961106 SAMEA7200887 4598STDY7805238_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412682 E-MTAB-94021598011819:4598STDY7805239_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961107 SAMEA7200888 4598STDY7805239_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412683 E-MTAB-94021598011819:4598STDY7805240_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961108 SAMEA7200889 4598STDY7805240_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412684 E-MTAB-94021598011819:4598STDY7805241_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961109 SAMEA7200890 4598STDY7805241_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412685 E-MTAB-94021598011819:4598STDY7805242_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961110 SAMEA7200891 4598STDY7805242_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412686 E-MTAB-94021598011819:4598STDY7805243_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961111 SAMEA7200892 4598STDY7805243_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412687 E-MTAB-94021598011819:4598STDY7805244_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961112 SAMEA7200893 4598STDY7805244_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412688 E-MTAB-94021598011819:4598STDY7805245_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961113 SAMEA7200894 4598STDY7805245_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412689 E-MTAB-94021598011819:4598STDY7805246_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961114 SAMEA7200895 4598STDY7805246_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412690 E-MTAB-94021598011819:4598STDY7805247_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961115 SAMEA7200896 4598STDY7805247_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412691 E-MTAB-94021598011819:4598STDY7805248_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961116 SAMEA7200897 4598STDY7805248_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412692 E-MTAB-94021598011819:4598STDY7805249_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961117 SAMEA7200898 4598STDY7805249_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412693 E-MTAB-94021598011819:4598STDY7805250_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961118 SAMEA7200899 4598STDY7805250_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412694 E-MTAB-94021598011819:4598STDY7805251_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961119 SAMEA7200900 4598STDY7805251_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412695 E-MTAB-94021598011819:4598STDY7805252_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961120 SAMEA7200901 4598STDY7805252_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412696 E-MTAB-94021598011819:4598STDY7805253_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961121 SAMEA7200902 4598STDY7805253_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412697 E-MTAB-94021598011819:4598STDY7805254_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961122 SAMEA7200903 4598STDY7805254_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412698 E-MTAB-94021598011819:4598STDY7805255_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961123 SAMEA7200904 4598STDY7805255_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412699 E-MTAB-94021598011819:4598STDY7805256_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961124 SAMEA7200905 4598STDY7805256_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412700 E-MTAB-94021598011819:4598STDY7805257_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961125 SAMEA7200906 4598STDY7805257_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412701 E-MTAB-94021598011819:4598STDY7805258_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961126 SAMEA7200907 4598STDY7805258_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412702 E-MTAB-94021598011819:4598STDY7805259_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961127 SAMEA7200908 4598STDY7805259_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412703 E-MTAB-94021598011819:4598STDY7805260_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961128 SAMEA7200909 4598STDY7805260_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412704 E-MTAB-94021598011819:4598STDY7805261_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961129 SAMEA7200910 4598STDY7805261_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412705 E-MTAB-94021598011819:4598STDY7805262_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961130 SAMEA7200911 4598STDY7805262_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412706 E-MTAB-94021598011819:4598STDY7805263_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961131 SAMEA7200912 4598STDY7805263_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412707 E-MTAB-94021598011819:4598STDY7805264_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961132 SAMEA7200913 4598STDY7805264_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412708 E-MTAB-94021598011819:4598STDY7805265_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961133 SAMEA7200914 4598STDY7805265_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412709 E-MTAB-94021598011819:4598STDY7805266_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961134 SAMEA7200915 4598STDY7805266_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412710 E-MTAB-94021598011819:4598STDY7805267_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961135 SAMEA7200916 4598STDY7805267_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412711 E-MTAB-94021598011819:4598STDY7805268_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961136 SAMEA7200917 4598STDY7805268_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412712 E-MTAB-94021598011819:4598STDY7805269_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961137 SAMEA7200918 4598STDY7805269_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412713 E-MTAB-94021598011819:4598STDY7805270_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961138 SAMEA7200919 4598STDY7805270_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412714 E-MTAB-94021598011819:4598STDY7805271_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961139 SAMEA7200920 4598STDY7805271_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412715 E-MTAB-94021598011819:4598STDY7805272_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961140 SAMEA7200921 4598STDY7805272_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412716 E-MTAB-94021598011819:4598STDY7805273_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961141 SAMEA7200922 4598STDY7805273_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412717 E-MTAB-94021598011819:4598STDY7805274_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961400 SAMEA7201186 4598STDY7805274_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412718 E-MTAB-94021598011819:4598STDY7805275_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961401 SAMEA7201187 4598STDY7805275_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412719 E-MTAB-94021598011819:4598STDY7805276_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961402 SAMEA7201188 4598STDY7805276_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412720 E-MTAB-94021598011819:4598STDY7805277_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961403 SAMEA7201189 4598STDY7805277_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412721 E-MTAB-94021598011819:4598STDY7805278_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961404 SAMEA7201190 4598STDY7805278_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412722 E-MTAB-94021598011819:4598STDY7805279_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961405 SAMEA7201191 4598STDY7805279_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412723 E-MTAB-94021598011819:4598STDY7805280_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961406 SAMEA7201192 4598STDY7805280_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412724 E-MTAB-94021598011819:4598STDY7805281_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961407 SAMEA7201193 4598STDY7805281_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412725 E-MTAB-94021598011819:4598STDY7805282_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961408 SAMEA7201194 4598STDY7805282_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412726 E-MTAB-94021598011819:4598STDY7805283_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961409 SAMEA7201195 4598STDY7805283_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412727 E-MTAB-94021598011819:4598STDY7805284_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961410 SAMEA7201196 4598STDY7805284_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412728 E-MTAB-94021598011819:4598STDY7805285_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961411 SAMEA7201197 4598STDY7805285_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412729 E-MTAB-94021598011819:4598STDY7805286_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961412 SAMEA7201198 4598STDY7805286_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412730 E-MTAB-94021598011819:4598STDY7805287_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961413 SAMEA7201199 4598STDY7805287_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412731 E-MTAB-94021598011819:4598STDY7805288_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961414 SAMEA7201200 4598STDY7805288_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412732 E-MTAB-94021598011819:4598STDY7805289_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961415 SAMEA7201201 4598STDY7805289_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412733 E-MTAB-94021598011819:4598STDY7805290_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961416 SAMEA7201202 4598STDY7805290_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412734 E-MTAB-94021598011819:4598STDY7805291_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961417 SAMEA7201203 4598STDY7805291_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412735 E-MTAB-94021598011819:4598STDY7805292_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961418 SAMEA7201204 4598STDY7805292_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412736 E-MTAB-94021598011819:4598STDY7805293_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961419 SAMEA7201205 4598STDY7805293_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412737 E-MTAB-94021598011819:4598STDY7805294_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961420 SAMEA7201206 4598STDY7805294_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412738 E-MTAB-94021598011819:4598STDY7805295_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961421 SAMEA7201207 4598STDY7805295_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412739 E-MTAB-94021598011819:4598STDY7805296_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961422 SAMEA7201208 4598STDY7805296_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412740 E-MTAB-94021598011819:4598STDY7805297_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961423 SAMEA7201209 4598STDY7805297_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412741 E-MTAB-94021598011819:4598STDY7805298_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961424 SAMEA7201210 4598STDY7805298_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412742 E-MTAB-94021598011819:4598STDY7805299_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961425 SAMEA7201211 4598STDY7805299_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412743 E-MTAB-94021598011819:4598STDY7805300_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961426 SAMEA7201212 4598STDY7805300_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412744 E-MTAB-94021598011819:4598STDY7805301_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961427 SAMEA7201213 4598STDY7805301_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412745 E-MTAB-94021598011819:4598STDY7805302_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961428 SAMEA7201214 4598STDY7805302_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412746 E-MTAB-94021598011819:4598STDY7805303_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961429 SAMEA7201215 4598STDY7805303_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412747 E-MTAB-94021598011819:4598STDY7805304_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961430 SAMEA7201216 4598STDY7805304_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412748 E-MTAB-94021598011819:4598STDY7805305_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961431 SAMEA7201217 4598STDY7805305_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412749 E-MTAB-94021598011819:4598STDY7805306_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961432 SAMEA7201218 4598STDY7805306_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412750 E-MTAB-94021598011819:4598STDY7805307_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961433 SAMEA7201219 4598STDY7805307_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412751 E-MTAB-94021598011819:4598STDY7805308_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961434 SAMEA7201220 4598STDY7805308_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412752 E-MTAB-94021598011819:4598STDY7805309_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961435 SAMEA7201221 4598STDY7805309_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412753 E-MTAB-94021598011819:4598STDY7805310_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961436 SAMEA7201222 4598STDY7805310_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412754 E-MTAB-94021598011819:4598STDY7805311_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961437 SAMEA7201223 4598STDY7805311_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412755 E-MTAB-94021598011819:4598STDY7805312_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961438 SAMEA7201224 4598STDY7805312_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412756 E-MTAB-94021598011819:4598STDY7805313_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961439 SAMEA7201225 4598STDY7805313_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412757 E-MTAB-94021598011819:4598STDY7805314_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961440 SAMEA7201226 4598STDY7805314_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412758 E-MTAB-94021598011819:4598STDY7805315_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961441 SAMEA7201227 4598STDY7805315_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412759 E-MTAB-94021598011819:4598STDY7805316_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961442 SAMEA7201228 4598STDY7805316_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412760 E-MTAB-94021598011819:4598STDY7805317_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961443 SAMEA7201229 4598STDY7805317_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412761 E-MTAB-94021598011819:4598STDY7805318_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961444 SAMEA7201230 4598STDY7805318_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412762 E-MTAB-94021598011819:4598STDY7805319_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961445 SAMEA7201231 4598STDY7805319_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412763 E-MTAB-94021598011819:4598STDY7805320_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961446 SAMEA7201232 4598STDY7805320_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412764 E-MTAB-94021598011819:4598STDY7805321_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961447 SAMEA7201233 4598STDY7805321_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412765 E-MTAB-94021598011819:4598STDY7805322_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961448 SAMEA7201234 4598STDY7805322_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412766 E-MTAB-94021598011819:4598STDY7805323_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961449 SAMEA7201235 4598STDY7805323_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412767 E-MTAB-94021598011819:4598STDY7805324_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961450 SAMEA7201236 4598STDY7805324_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412768 E-MTAB-94021598011819:4598STDY7805325_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961451 SAMEA7201237 4598STDY7805325_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412769 E-MTAB-94021598011819:4598STDY7805326_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961452 SAMEA7201238 4598STDY7805326_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412770 E-MTAB-94021598011819:4598STDY7805327_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961453 SAMEA7201239 4598STDY7805327_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412771 E-MTAB-94021598011819:4598STDY7805328_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961454 SAMEA7201240 4598STDY7805328_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412772 E-MTAB-94021598011819:4598STDY7805329_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961455 SAMEA7201241 4598STDY7805329_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412773 E-MTAB-94021598011819:4598STDY7805330_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961456 SAMEA7201242 4598STDY7805330_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412774 E-MTAB-94021598011819:4598STDY7805331_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961457 SAMEA7201243 4598STDY7805331_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412775 E-MTAB-94021598011819:4598STDY7805332_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961458 SAMEA7201244 4598STDY7805332_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412776 E-MTAB-94021598011819:4598STDY7805333_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961459 SAMEA7201245 4598STDY7805333_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412777 E-MTAB-94021598011819:4598STDY7805334_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961460 SAMEA7201246 4598STDY7805334_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412778 E-MTAB-94021598011819:4598STDY7805335_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961461 SAMEA7201247 4598STDY7805335_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412779 E-MTAB-94021598011819:4598STDY7805336_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961462 SAMEA7201248 4598STDY7805336_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412780 E-MTAB-94021598011819:4598STDY7805337_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961463 SAMEA7201249 4598STDY7805337_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412781 E-MTAB-94021598011819:4598STDY7805338_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961464 SAMEA7201250 4598STDY7805338_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412782 E-MTAB-94021598011819:4598STDY7805339_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961465 SAMEA7201251 4598STDY7805339_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412783 E-MTAB-94021598011819:4598STDY7805340_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961466 SAMEA7201252 4598STDY7805340_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412784 E-MTAB-94021598011819:4598STDY7805341_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961467 SAMEA7201253 4598STDY7805341_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412785 E-MTAB-94021598011819:4598STDY7805342_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961468 SAMEA7201254 4598STDY7805342_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412786 E-MTAB-94021598011819:4598STDY7805343_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961469 SAMEA7201255 4598STDY7805343_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412787 E-MTAB-94021598011819:4598STDY7805344_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961470 SAMEA7201256 4598STDY7805344_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412788 E-MTAB-94021598011819:4598STDY7805345_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961471 SAMEA7201257 4598STDY7805345_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412789 E-MTAB-94021598011819:4598STDY7805346_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961472 SAMEA7201258 4598STDY7805346_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412790 E-MTAB-94021598011819:4598STDY7805347_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961473 SAMEA7201259 4598STDY7805347_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 7 Experimental Factor: compound none ERX4412791 E-MTAB-94021598011819:4598STDY7805348_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961474 SAMEA7201260 4598STDY7805348_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412792 E-MTAB-94021598011819:4598STDY7805349_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961475 SAMEA7201261 4598STDY7805349_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412793 E-MTAB-94021598011819:4598STDY7805350_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961476 SAMEA7201262 4598STDY7805350_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412794 E-MTAB-94021598011819:4598STDY7805351_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961477 SAMEA7201263 4598STDY7805351_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412795 E-MTAB-94021598011819:4598STDY7805352_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961478 SAMEA7201264 4598STDY7805352_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412796 E-MTAB-94021598011819:4598STDY7805353_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961479 SAMEA7201265 4598STDY7805353_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412797 E-MTAB-94021598011819:4598STDY7805354_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961480 SAMEA7201266 4598STDY7805354_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412798 E-MTAB-94021598011819:4598STDY7805355_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961481 SAMEA7201267 4598STDY7805355_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412799 E-MTAB-94021598011819:4598STDY7805356_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961482 SAMEA7201268 4598STDY7805356_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412800 E-MTAB-94021598011819:4598STDY7805357_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961483 SAMEA7201269 4598STDY7805357_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412801 E-MTAB-94021598011819:4598STDY7805358_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961484 SAMEA7201270 4598STDY7805358_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412802 E-MTAB-94021598011819:4598STDY7805359_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961485 SAMEA7201271 4598STDY7805359_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412803 E-MTAB-94021598011819:4598STDY7805360_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961486 SAMEA7201272 4598STDY7805360_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412804 E-MTAB-94021598011819:4598STDY7805361_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961487 SAMEA7201273 4598STDY7805361_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412805 E-MTAB-94021598011819:4598STDY7805362_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961488 SAMEA7201274 4598STDY7805362_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412806 E-MTAB-94021598011819:4598STDY7805363_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961489 SAMEA7201275 4598STDY7805363_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412807 E-MTAB-94021598011819:4598STDY7805364_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961490 SAMEA7201276 4598STDY7805364_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412808 E-MTAB-94021598011819:4598STDY7805365_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961491 SAMEA7201277 4598STDY7805365_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412809 E-MTAB-94021598011819:4598STDY7805366_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961492 SAMEA7201278 4598STDY7805366_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412810 E-MTAB-94021598011819:4598STDY7805367_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961493 SAMEA7201279 4598STDY7805367_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412811 E-MTAB-94021598011819:4598STDY7805368_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961494 SAMEA7201280 4598STDY7805368_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412812 E-MTAB-94021598011819:4598STDY7805369_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961495 SAMEA7201281 4598STDY7805369_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412813 E-MTAB-94021598011819:4598STDY7805370_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961496 SAMEA7201282 4598STDY7805370_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412814 E-MTAB-94021598011819:4598STDY7805371_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961497 SAMEA7201283 4598STDY7805371_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412815 E-MTAB-94021598011819:4598STDY7805372_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961498 SAMEA7201284 4598STDY7805372_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412816 E-MTAB-94021598011819:4598STDY7805373_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961499 SAMEA7201285 4598STDY7805373_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412817 E-MTAB-94021598011819:4598STDY7805374_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961500 SAMEA7201286 4598STDY7805374_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412818 E-MTAB-94021598011819:4598STDY7805375_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961501 SAMEA7201287 4598STDY7805375_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412819 E-MTAB-94021598011819:4598STDY7805376_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961502 SAMEA7201288 4598STDY7805376_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412820 E-MTAB-94021598011819:4598STDY7805377_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961503 SAMEA7201289 4598STDY7805377_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412821 E-MTAB-94021598011819:4598STDY7805378_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961504 SAMEA7201290 4598STDY7805378_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412822 E-MTAB-94021598011819:4598STDY7805379_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961505 SAMEA7201291 4598STDY7805379_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412823 E-MTAB-94021598011819:4598STDY7805380_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961506 SAMEA7201292 4598STDY7805380_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412824 E-MTAB-94021598011819:4598STDY7805381_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961507 SAMEA7201293 4598STDY7805381_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412825 E-MTAB-94021598011819:4598STDY7805382_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961508 SAMEA7201294 4598STDY7805382_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412826 E-MTAB-94021598011819:4598STDY7805383_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961509 SAMEA7201295 4598STDY7805383_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412827 E-MTAB-94021598011819:4598STDY7805384_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961510 SAMEA7201296 4598STDY7805384_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412828 E-MTAB-94021598011819:4598STDY7805385_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961511 SAMEA7201297 4598STDY7805385_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412829 E-MTAB-94021598011819:4598STDY7805386_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961512 SAMEA7201298 4598STDY7805386_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412830 E-MTAB-94021598011819:4598STDY7805387_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961513 SAMEA7201299 4598STDY7805387_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412831 E-MTAB-94021598011819:4598STDY7805388_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961514 SAMEA7201300 4598STDY7805388_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412832 E-MTAB-94021598011819:4598STDY7805389_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961515 SAMEA7201301 4598STDY7805389_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412833 E-MTAB-94021598011819:4598STDY7805390_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961516 SAMEA7201302 4598STDY7805390_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412834 E-MTAB-94021598011819:4598STDY7805391_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961517 SAMEA7201303 4598STDY7805391_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412835 E-MTAB-94021598011819:4598STDY7805392_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961518 SAMEA7201304 4598STDY7805392_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412836 E-MTAB-94021598011819:4598STDY7805393_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961519 SAMEA7201305 4598STDY7805393_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412837 E-MTAB-94021598011819:4598STDY7805394_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961520 SAMEA7201306 4598STDY7805394_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412838 E-MTAB-94021598011819:4598STDY7805395_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961521 SAMEA7201307 4598STDY7805395_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412839 E-MTAB-94021598011819:4598STDY7805396_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961522 SAMEA7201308 4598STDY7805396_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412840 E-MTAB-94021598011819:4598STDY7805397_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961523 SAMEA7201309 4598STDY7805397_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412841 E-MTAB-94021598011819:4598STDY7805398_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961524 SAMEA7201310 4598STDY7805398_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412842 E-MTAB-94021598011819:4598STDY7805399_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961525 SAMEA7201311 4598STDY7805399_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412843 E-MTAB-94021598011819:4598STDY7805400_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961526 SAMEA7201312 4598STDY7805400_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412844 E-MTAB-94021598011819:4598STDY7805401_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961527 SAMEA7201313 4598STDY7805401_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412845 E-MTAB-94021598011819:4598STDY7805402_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961528 SAMEA7201314 4598STDY7805402_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412846 E-MTAB-94021598011819:4598STDY7805403_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961529 SAMEA7201315 4598STDY7805403_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412847 E-MTAB-94021598011819:4598STDY7805404_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961530 SAMEA7201316 4598STDY7805404_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412848 E-MTAB-94021598011819:4598STDY7805405_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961531 SAMEA7201317 4598STDY7805405_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412849 E-MTAB-94021598011819:4598STDY7805406_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961532 SAMEA7201318 4598STDY7805406_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412850 E-MTAB-94021598011819:4598STDY7805407_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961533 SAMEA7201319 4598STDY7805407_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412851 E-MTAB-94021598011819:4598STDY7805408_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961534 SAMEA7201320 4598STDY7805408_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412852 E-MTAB-94021598011819:4598STDY7805409_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961535 SAMEA7201321 4598STDY7805409_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412853 E-MTAB-94021598011819:4598STDY7805410_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961536 SAMEA7201322 4598STDY7805410_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412854 E-MTAB-94021598011819:4598STDY7805411_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961537 SAMEA7201323 4598STDY7805411_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412855 E-MTAB-94021598011819:4598STDY7805412_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961538 SAMEA7201324 4598STDY7805412_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412856 E-MTAB-94021598011819:4598STDY7805413_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961539 SAMEA7201325 4598STDY7805413_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412857 E-MTAB-94021598011819:4598STDY7805414_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961540 SAMEA7201326 4598STDY7805414_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412858 E-MTAB-94021598011819:4598STDY7805415_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961541 SAMEA7201327 4598STDY7805415_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412859 E-MTAB-94021598011819:4598STDY7805416_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961542 SAMEA7201328 4598STDY7805416_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412860 E-MTAB-94021598011819:4598STDY7805417_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961543 SAMEA7201329 4598STDY7805417_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412861 E-MTAB-94021598011819:4598STDY7805418_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961544 SAMEA7201330 4598STDY7805418_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412862 E-MTAB-94021598011819:4598STDY7805419_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961545 SAMEA7201331 4598STDY7805419_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412863 E-MTAB-94021598011819:4598STDY7805420_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961546 SAMEA7201332 4598STDY7805420_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412864 E-MTAB-94021598011819:4598STDY7805421_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961547 SAMEA7201333 4598STDY7805421_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412865 E-MTAB-94021598011819:4598STDY7805422_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961548 SAMEA7201334 4598STDY7805422_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412866 E-MTAB-94021598011819:4598STDY7805423_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961549 SAMEA7201335 4598STDY7805423_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412867 E-MTAB-94021598011819:4598STDY7805424_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961550 SAMEA7201336 4598STDY7805424_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412868 E-MTAB-94021598011819:4598STDY7805425_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961551 SAMEA7201337 4598STDY7805425_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412869 E-MTAB-94021598011819:4598STDY7805426_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961552 SAMEA7201338 4598STDY7805426_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412870 E-MTAB-94021598011819:4598STDY7805427_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961553 SAMEA7201339 4598STDY7805427_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412871 E-MTAB-94021598011819:4598STDY7805428_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961554 SAMEA7201340 4598STDY7805428_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412872 E-MTAB-94021598011819:4598STDY7805429_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961555 SAMEA7201341 4598STDY7805429_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412873 E-MTAB-94021598011819:4598STDY7805430_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961556 SAMEA7201342 4598STDY7805430_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412874 E-MTAB-94021598011819:4598STDY7805431_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961557 SAMEA7201343 4598STDY7805431_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412875 E-MTAB-94021598011819:4598STDY7805432_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961558 SAMEA7201344 4598STDY7805432_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412876 E-MTAB-94021598011819:4598STDY7805433_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961559 SAMEA7201345 4598STDY7805433_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412877 E-MTAB-94021598011819:4598STDY7805434_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961560 SAMEA7201346 4598STDY7805434_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412878 E-MTAB-94021598011819:4598STDY7805435_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961561 SAMEA7201347 4598STDY7805435_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412879 E-MTAB-94021598011819:4598STDY7805436_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961562 SAMEA7201348 4598STDY7805436_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412880 E-MTAB-94021598011819:4598STDY7805437_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961563 SAMEA7201349 4598STDY7805437_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412881 E-MTAB-94021598011819:4598STDY7805438_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961564 SAMEA7201350 4598STDY7805438_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412882 E-MTAB-94021598011819:4598STDY7805439_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961565 SAMEA7201351 4598STDY7805439_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412883 E-MTAB-94021598011819:4598STDY7805440_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961566 SAMEA7201352 4598STDY7805440_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412884 E-MTAB-94021598011819:4598STDY7805441_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961567 SAMEA7201353 4598STDY7805441_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412885 E-MTAB-94021598011819:4598STDY7805442_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961568 SAMEA7201354 4598STDY7805442_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412886 E-MTAB-94021598011819:4598STDY7805443_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961569 SAMEA7201355 4598STDY7805443_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412887 E-MTAB-94021598011819:4598STDY7805444_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961570 SAMEA7201356 4598STDY7805444_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412888 E-MTAB-94021598011819:4598STDY7805445_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961571 SAMEA7201357 4598STDY7805445_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412889 E-MTAB-94021598011819:4598STDY7805446_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961572 SAMEA7201358 4598STDY7805446_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412890 E-MTAB-94021598011819:4598STDY7805447_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961573 SAMEA7201359 4598STDY7805447_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412891 E-MTAB-94021598011819:4598STDY7805448_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961574 SAMEA7201360 4598STDY7805448_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412892 E-MTAB-94021598011819:4598STDY7805449_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961575 SAMEA7201361 4598STDY7805449_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412893 E-MTAB-94021598011819:4598STDY7805450_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961576 SAMEA7201362 4598STDY7805450_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412894 E-MTAB-94021598011819:4598STDY7805451_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961577 SAMEA7201363 4598STDY7805451_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412895 E-MTAB-94021598011819:4598STDY7805452_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961578 SAMEA7201364 4598STDY7805452_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412896 E-MTAB-94021598011819:4598STDY7805453_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961579 SAMEA7201365 4598STDY7805453_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412897 E-MTAB-94021598011819:4598STDY7805454_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961580 SAMEA7201366 4598STDY7805454_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412898 E-MTAB-94021598011819:4598STDY7805455_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961581 SAMEA7201367 4598STDY7805455_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412899 E-MTAB-94021598011819:4598STDY7805456_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961582 SAMEA7201368 4598STDY7805456_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412900 E-MTAB-94021598011819:4598STDY7805457_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961583 SAMEA7201369 4598STDY7805457_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412901 E-MTAB-94021598011819:4598STDY7805458_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961584 SAMEA7201370 4598STDY7805458_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412902 E-MTAB-94021598011819:4598STDY7805459_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961585 SAMEA7201371 4598STDY7805459_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412903 E-MTAB-94021598011819:4598STDY7805460_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961586 SAMEA7201372 4598STDY7805460_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412904 E-MTAB-94021598011819:4598STDY7805461_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961587 SAMEA7201373 4598STDY7805461_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412905 E-MTAB-94021598011819:4598STDY7805462_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961588 SAMEA7201374 4598STDY7805462_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412906 E-MTAB-94021598011819:4598STDY7805463_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961589 SAMEA7201375 4598STDY7805463_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412907 E-MTAB-94021598011819:4598STDY7805464_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961590 SAMEA7201376 4598STDY7805464_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412908 E-MTAB-94021598011819:4598STDY7805465_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961591 SAMEA7201377 4598STDY7805465_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412909 E-MTAB-94021598011819:4598STDY7805466_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961592 SAMEA7201378 4598STDY7805466_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412910 E-MTAB-94021598011819:4598STDY7805467_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961593 SAMEA7201379 4598STDY7805467_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412911 E-MTAB-94021598011819:4598STDY7805468_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961594 SAMEA7201380 4598STDY7805468_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412912 E-MTAB-94021598011819:4598STDY7805469_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961595 SAMEA7201381 4598STDY7805469_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412913 E-MTAB-94021598011819:4598STDY7805470_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961596 SAMEA7201382 4598STDY7805470_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412914 E-MTAB-94021598011819:4598STDY7805471_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961597 SAMEA7201383 4598STDY7805471_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412915 E-MTAB-94021598011819:4598STDY7805472_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961598 SAMEA7201384 4598STDY7805472_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412916 E-MTAB-94021598011819:4598STDY7805473_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961599 SAMEA7201385 4598STDY7805473_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412917 E-MTAB-94021598011819:4598STDY7805474_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961600 SAMEA7201386 4598STDY7805474_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412918 E-MTAB-94021598011819:4598STDY7805475_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961601 SAMEA7201387 4598STDY7805475_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412919 E-MTAB-94021598011819:4598STDY7805476_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961602 SAMEA7201388 4598STDY7805476_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412920 E-MTAB-94021598011819:4598STDY7805477_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961603 SAMEA7201389 4598STDY7805477_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412921 E-MTAB-94021598011819:4598STDY7805478_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961604 SAMEA7201390 4598STDY7805478_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412922 E-MTAB-94021598011819:4598STDY7805479_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961605 SAMEA7201391 4598STDY7805479_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412923 E-MTAB-94021598011819:4598STDY7805480_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961606 SAMEA7201392 4598STDY7805480_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412924 E-MTAB-94021598011819:4598STDY7805481_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961607 SAMEA7201393 4598STDY7805481_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412925 E-MTAB-94021598011819:4598STDY7805482_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961608 SAMEA7201394 4598STDY7805482_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412926 E-MTAB-94021598011819:4598STDY7805483_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961609 SAMEA7201395 4598STDY7805483_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412927 E-MTAB-94021598011819:4598STDY7805484_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961610 SAMEA7201396 4598STDY7805484_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412928 E-MTAB-94021598011819:4598STDY7805485_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961611 SAMEA7201397 4598STDY7805485_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412929 E-MTAB-94021598011819:4598STDY7805486_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961612 SAMEA7201398 4598STDY7805486_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412930 E-MTAB-94021598011819:4598STDY7805487_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961613 SAMEA7201399 4598STDY7805487_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412931 E-MTAB-94021598011819:4598STDY7805488_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961614 SAMEA7201400 4598STDY7805488_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412932 E-MTAB-94021598011819:4598STDY7805489_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961615 SAMEA7201401 4598STDY7805489_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412933 E-MTAB-94021598011819:4598STDY7805490_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961616 SAMEA7201402 4598STDY7805490_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412934 E-MTAB-94021598011819:4598STDY7805491_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961617 SAMEA7201403 4598STDY7805491_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412935 E-MTAB-94021598011819:4598STDY7805492_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961618 SAMEA7201404 4598STDY7805492_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412936 E-MTAB-94021598011819:4598STDY7805493_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961619 SAMEA7201405 4598STDY7805493_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412937 E-MTAB-94021598011819:4598STDY7805494_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961620 SAMEA7201406 4598STDY7805494_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412938 E-MTAB-94021598011819:4598STDY7805495_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961621 SAMEA7201407 4598STDY7805495_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412939 E-MTAB-94021598011819:4598STDY7805496_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961622 SAMEA7201408 4598STDY7805496_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412940 E-MTAB-94021598011819:4598STDY7805497_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961623 SAMEA7201409 4598STDY7805497_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412941 E-MTAB-94021598011819:4598STDY7805498_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961624 SAMEA7201410 4598STDY7805498_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412942 E-MTAB-94021598011819:4598STDY7805499_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961625 SAMEA7201411 4598STDY7805499_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412943 E-MTAB-94021598011819:4598STDY7805500_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961626 SAMEA7201412 4598STDY7805500_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412944 E-MTAB-94021598011819:4598STDY7805501_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961627 SAMEA7201413 4598STDY7805501_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412945 E-MTAB-94021598011819:4598STDY7805502_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961628 SAMEA7201414 4598STDY7805502_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412946 E-MTAB-94021598011819:4598STDY7805503_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961629 SAMEA7201415 4598STDY7805503_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412947 E-MTAB-94021598011819:4598STDY7805504_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961630 SAMEA7201416 4598STDY7805504_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412948 E-MTAB-94021598011819:4598STDY7805505_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961631 SAMEA7201417 4598STDY7805505_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412949 E-MTAB-94021598011819:4598STDY7805506_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961632 SAMEA7201418 4598STDY7805506_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412950 E-MTAB-94021598011819:4598STDY7805507_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961633 SAMEA7201419 4598STDY7805507_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412951 E-MTAB-94021598011819:4598STDY7805508_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961634 SAMEA7201420 4598STDY7805508_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412952 E-MTAB-94021598011819:4598STDY7805509_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961635 SAMEA7201421 4598STDY7805509_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412953 E-MTAB-94021598011819:4598STDY7805510_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961636 SAMEA7201422 4598STDY7805510_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412954 E-MTAB-94021598011819:4598STDY7805511_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961637 SAMEA7201423 4598STDY7805511_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412955 E-MTAB-94021598011819:4598STDY7805512_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961638 SAMEA7201424 4598STDY7805512_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412956 E-MTAB-94021598011819:4598STDY7805513_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961639 SAMEA7201425 4598STDY7805513_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412957 E-MTAB-94021598011819:4598STDY7805514_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961640 SAMEA7201426 4598STDY7805514_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412958 E-MTAB-94021598011819:4598STDY7805515_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961641 SAMEA7201427 4598STDY7805515_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412959 E-MTAB-94021598011819:4598STDY7805516_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961642 SAMEA7201428 4598STDY7805516_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412960 E-MTAB-94021598011819:4598STDY7805517_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961643 SAMEA7201429 4598STDY7805517_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412961 E-MTAB-94021598011819:4598STDY7805518_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961644 SAMEA7201430 4598STDY7805518_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412962 E-MTAB-94021598011819:4598STDY7805519_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961645 SAMEA7201431 4598STDY7805519_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412963 E-MTAB-94021598011819:4598STDY7805520_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961646 SAMEA7201432 4598STDY7805520_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412964 E-MTAB-94021598011819:4598STDY7805521_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961647 SAMEA7201433 4598STDY7805521_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412965 E-MTAB-94021598011819:4598STDY7805522_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961648 SAMEA7201434 4598STDY7805522_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412966 E-MTAB-94021598011819:4598STDY7805523_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961649 SAMEA7201435 4598STDY7805523_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412967 E-MTAB-94021598011819:4598STDY7805524_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961650 SAMEA7201436 4598STDY7805524_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412968 E-MTAB-94021598011819:4598STDY7805525_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961651 SAMEA7201437 4598STDY7805525_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412969 E-MTAB-94021598011819:4598STDY7805526_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961652 SAMEA7201438 4598STDY7805526_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412970 E-MTAB-94021598011819:4598STDY7805527_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961653 SAMEA7201439 4598STDY7805527_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412971 E-MTAB-94021598011819:4598STDY7805528_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961654 SAMEA7201440 4598STDY7805528_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412972 E-MTAB-94021598011819:4598STDY7805529_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961655 SAMEA7201441 4598STDY7805529_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412973 E-MTAB-94021598011819:4598STDY7805530_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961656 SAMEA7201442 4598STDY7805530_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412974 E-MTAB-94021598011819:4598STDY7805531_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961657 SAMEA7201443 4598STDY7805531_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412975 E-MTAB-94021598011819:4598STDY7805532_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961658 SAMEA7201444 4598STDY7805532_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412976 E-MTAB-94021598011819:4598STDY7805533_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961659 SAMEA7201445 4598STDY7805533_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412977 E-MTAB-94021598011819:4598STDY7805534_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961660 SAMEA7201446 4598STDY7805534_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412978 E-MTAB-94021598011819:4598STDY7805535_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961661 SAMEA7201447 4598STDY7805535_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412979 E-MTAB-94021598011819:4598STDY7805536_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961662 SAMEA7201448 4598STDY7805536_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412980 E-MTAB-94021598011819:4598STDY7805537_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961663 SAMEA7201449 4598STDY7805537_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412981 E-MTAB-94021598011819:4598STDY7805538_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961664 SAMEA7201450 4598STDY7805538_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412982 E-MTAB-94021598011819:4598STDY7805539_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961665 SAMEA7201451 4598STDY7805539_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412983 E-MTAB-94021598011819:4598STDY7805540_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961666 SAMEA7201452 4598STDY7805540_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412984 E-MTAB-94021598011819:4598STDY7805541_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961667 SAMEA7201453 4598STDY7805541_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412985 E-MTAB-94021598011819:4598STDY7805542_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961668 SAMEA7201454 4598STDY7805542_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412986 E-MTAB-94021598011819:4598STDY7805543_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961669 SAMEA7201455 4598STDY7805543_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412987 E-MTAB-94021598011819:4598STDY7805544_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961670 SAMEA7201456 4598STDY7805544_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412988 E-MTAB-94021598011819:4598STDY7805545_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961671 SAMEA7201457 4598STDY7805545_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412989 E-MTAB-94021598011819:4598STDY7805546_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961672 SAMEA7201458 4598STDY7805546_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412990 E-MTAB-94021598011819:4598STDY7805547_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961673 SAMEA7201459 4598STDY7805547_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412991 E-MTAB-94021598011819:4598STDY7805548_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961674 SAMEA7201460 4598STDY7805548_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412992 E-MTAB-94021598011819:4598STDY7805549_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961675 SAMEA7201461 4598STDY7805549_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412993 E-MTAB-94021598011819:4598STDY7805550_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961676 SAMEA7201462 4598STDY7805550_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412994 E-MTAB-94021598011819:4598STDY7805551_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961677 SAMEA7201463 4598STDY7805551_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412995 E-MTAB-94021598011819:4598STDY7805552_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961678 SAMEA7201464 4598STDY7805552_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412996 E-MTAB-94021598011819:4598STDY7805553_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961679 SAMEA7201465 4598STDY7805553_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412997 E-MTAB-94021598011819:4598STDY7805554_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961680 SAMEA7201466 4598STDY7805554_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412998 E-MTAB-94021598011819:4598STDY7805555_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961681 SAMEA7201467 4598STDY7805555_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4412999 E-MTAB-94021598011819:4598STDY7805556_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961682 SAMEA7201468 4598STDY7805556_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413000 E-MTAB-94021598011819:4598STDY7805557_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961683 SAMEA7201469 4598STDY7805557_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413001 E-MTAB-94021598011819:4598STDY7805558_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961684 SAMEA7201470 4598STDY7805558_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413002 E-MTAB-94021598011819:4598STDY7805559_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961685 SAMEA7201471 4598STDY7805559_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413003 E-MTAB-94021598011819:4598STDY7805560_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961686 SAMEA7201472 4598STDY7805560_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413004 E-MTAB-94021598011819:4598STDY7805561_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961687 SAMEA7201473 4598STDY7805561_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413005 E-MTAB-94021598011819:4598STDY7805562_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961688 SAMEA7201474 4598STDY7805562_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413006 E-MTAB-94021598011819:4598STDY7805563_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961689 SAMEA7201475 4598STDY7805563_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413007 E-MTAB-94021598011819:4598STDY7805564_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961690 SAMEA7201476 4598STDY7805564_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413008 E-MTAB-94021598011819:4598STDY7805565_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961691 SAMEA7201477 4598STDY7805565_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413009 E-MTAB-94021598011819:4598STDY7805566_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961692 SAMEA7201478 4598STDY7805566_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413010 E-MTAB-94021598011819:4598STDY7805567_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961693 SAMEA7201479 4598STDY7805567_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413011 E-MTAB-94021598011819:4598STDY7805568_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961694 SAMEA7201480 4598STDY7805568_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413012 E-MTAB-94021598011819:4598STDY7805569_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961695 SAMEA7201481 4598STDY7805569_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413013 E-MTAB-94021598011819:4598STDY7805570_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961696 SAMEA7201482 4598STDY7805570_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413014 E-MTAB-94021598011819:4598STDY7805571_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961697 SAMEA7201483 4598STDY7805571_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413015 E-MTAB-94021598011819:4598STDY7805572_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961698 SAMEA7201484 4598STDY7805572_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413016 E-MTAB-94021598011819:4598STDY7805573_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961699 SAMEA7201485 4598STDY7805573_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413017 E-MTAB-94021598011819:4598STDY7805574_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961700 SAMEA7201486 4598STDY7805574_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413018 E-MTAB-94021598011819:4598STDY7805575_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961701 SAMEA7201487 4598STDY7805575_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413019 E-MTAB-94021598011819:4598STDY7805576_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961702 SAMEA7201488 4598STDY7805576_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413020 E-MTAB-94021598011819:4598STDY7805577_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961703 SAMEA7201489 4598STDY7805577_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413021 E-MTAB-94021598011819:4598STDY7805578_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961704 SAMEA7201490 4598STDY7805578_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413022 E-MTAB-94021598011819:4598STDY7805579_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961705 SAMEA7201491 4598STDY7805579_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413023 E-MTAB-94021598011819:4598STDY7805580_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961706 SAMEA7201492 4598STDY7805580_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413024 E-MTAB-94021598011819:4598STDY7805581_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961707 SAMEA7201493 4598STDY7805581_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413025 E-MTAB-94021598011819:4598STDY7805582_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961708 SAMEA7201494 4598STDY7805582_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413026 E-MTAB-94021598011819:4598STDY7805583_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961709 SAMEA7201495 4598STDY7805583_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413027 E-MTAB-94021598011819:4598STDY7805584_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961710 SAMEA7201496 4598STDY7805584_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413028 E-MTAB-94021598011819:4598STDY7805585_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961711 SAMEA7201497 4598STDY7805585_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413029 E-MTAB-94021598011819:4598STDY7805586_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961712 SAMEA7201498 4598STDY7805586_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413030 E-MTAB-94021598011819:4598STDY7805587_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961713 SAMEA7201499 4598STDY7805587_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413031 E-MTAB-94021598011819:4598STDY7805588_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961714 SAMEA7201500 4598STDY7805588_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413032 E-MTAB-94021598011819:4598STDY7805589_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961715 SAMEA7201501 4598STDY7805589_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413033 E-MTAB-94021598011819:4598STDY7805590_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961716 SAMEA7201502 4598STDY7805590_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413034 E-MTAB-94021598011819:4598STDY7805591_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961717 SAMEA7201503 4598STDY7805591_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413035 E-MTAB-94021598011819:4598STDY7805592_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961718 SAMEA7201504 4598STDY7805592_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413036 E-MTAB-94021598011819:4598STDY7805593_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961719 SAMEA7201505 4598STDY7805593_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413037 E-MTAB-94021598011819:4598STDY7805594_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961720 SAMEA7201506 4598STDY7805594_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413038 E-MTAB-94021598011819:4598STDY7805595_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961721 SAMEA7201507 4598STDY7805595_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413039 E-MTAB-94021598011819:4598STDY7805596_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961722 SAMEA7201508 4598STDY7805596_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413040 E-MTAB-94021598011819:4598STDY7805597_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961723 SAMEA7201509 4598STDY7805597_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413041 E-MTAB-94021598011819:4598STDY7805598_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961724 SAMEA7201510 4598STDY7805598_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none ERX4413042 E-MTAB-94021598011819:4598STDY7805599_p ERP123562 PRJEB39979 scATAC-seq of mouse Plasmodium-specific CD4+ T cells ERS4961725 SAMEA7201511 4598STDY7805599_p ATAC-seq GENOMIC SINGLE CELL other Viable PbTII cells were FACS sorted from pooled splenic MACS-enriced CD4+ T cells. Raw ATAC-seq reads were mapped to mouse genome MGSCv37 (mm9) using BWA-MEM. Sorted cells were resuspended in 50 μl tagmentation mix (33 mM Tris-acetate, pH 7.8, 66 mM potassium acetate, 10 mM magnesium acetate, 16% dimethylformamide (DMF), 0.01% digitonin and 5 μl of Tn5 from the Nextera kit from Illumina, Cat. No. FC-121-1030). Cell/ tagmentation mixture was then incubated at 37°C, 800rpm on an Eppendorf thermomixer for 30 minutes. Tagmentation reaction was stopped by the addition of equal volume (50 μl) of stop buffer (10 mM Tris-HCl, pH 8.0, 20 mM EDTA, pH 8.0) followed by incubation in ice for 10 minutes. 150 uL of DPBS/ 0.5% BSA was added to the mixture and nuclei suspension was then transferred to a FACS tube. 0.0006% DAPI (in-house) was added for staining the nuclei prior to single-nuclei sort into 384-well plate (Eppendorf, Cat. No. 0030128508) containing 2 µl of 2X lysis buffer (100 mM Tris.HCl, pH 8.0, 100 mM NaCl, 40 µg/ml Proteinase K (New England BioLabs, P8107S), 0.4% SDS. Single-nuclei lysates were sealed and spun at 100 x g for 1 minute then immediately frozen on dry ice and stored at -80°C. Tn5 release and proteinase K digestion was then performed on a PCR machine (MJ Research Peltier Thermal Cycler) at 65°C for 15 minutes followed by the addition of 2 µl of 10% Tween to quench the SDS. 5 µl of NEBNext High-Fidelity 2X PCR Master Mix (New England Biolabs Inc, Cat. No. M0541L) was then added to a pre-prepared 384-well plate (Eppendorf, Cat. No. 0030128508) containing 1 µl of 10 µM i5 and i7 indexing primer mix (5 µM each) (Integrated DNA Technologies). The indexing primers were arranged in a combinatorial manner to allow multiplexing of up to 1536 (4x 384-well plates) sorted nuclei into one sequencing pool. The plate containing the PCR Master Mix and indexing primers was stamped onto the single nuclei, mixed briefly, sealed and spun at 100 x g for 1 minute. Amplification was performed on a PCR machine (MJ Research Peltier Thermal Cycler) with 72°C 10 min, 98°C 5 min, 20 cycles of [98°C 10 s, 63°C 30 s, 72°C 20 s]. The 384-well plate containing the PCR product was inverted into a VBLOK200 reservoir (Clickbio Cat. No. CBVBLOK200-1) and spun at 200 g for 1 minute. The combined reactions were then transferred to a 5 ml Eppendorf tube, (Eppendorf, Cat No. 0030119401) and the DNA purified, and size selected with an AMPure XP workflow (Beckman Coulter, Cat No. A63880). Illumina HiSeq 4000 Experimental Factor: infect Plasmodium chabaudi chabaudi (AS) Experimental Factor: time 4 Experimental Factor: compound none