SRX2212520 GSM2337202 SRP090876 SRS1729491 GSM2337202 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337202 GEO Accession GSM2337202 SRX2212521 GSM2337203 SRP090876 SRS1729492 GSM2337203 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337203 GEO Accession GSM2337203 SRX2212522 GSM2337204 SRP090876 SRS1729494 GSM2337204 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337204 GEO Accession GSM2337204 SRX2212523 GSM2337205 SRP090876 SRS1729493 GSM2337205 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337205 GEO Accession GSM2337205 SRX2212524 GSM2337206 SRP090876 SRS1729495 GSM2337206 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337206 GEO Accession GSM2337206 SRX2212525 GSM2337207 SRP090876 SRS1729496 GSM2337207 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337207 GEO Accession GSM2337207 SRX2212526 GSM2337208 SRP090876 SRS1729497 GSM2337208 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337208 GEO Accession GSM2337208 SRX2212527 GSM2337209 SRP090876 SRS1729498 GSM2337209 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337209 GEO Accession GSM2337209 SRX2212528 GSM2337210 SRP090876 SRS1729499 GSM2337210 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337210 GEO Accession GSM2337210 SRX2212529 GSM2337211 SRP090876 SRS1729500 GSM2337211 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337211 GEO Accession GSM2337211 SRX2212530 GSM2337212 SRP090876 SRS1729501 GSM2337212 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337212 GEO Accession GSM2337212 SRX2212531 GSM2337213 SRP090876 SRS1729502 GSM2337213 OTHER GENOMIC other All donor P14 cells were prepared from naive spleen using CD8 negative selection (Miltenyi Biotec). To generate effector, memory and exhausted CD8+ T cells, approximately 1-2 x 103 P14 cells were transferred into recipient mice, followed by LCMV infection one day later. Target effector/memory/exhausted P14 cells were harvested only from recipient spleens at d8 or d27 p.i. After enrichment using CD45.2 FITC Ab and anti-FITC microbes (Miltenyi), cells were stained and sorted by Aria II (BD). Naïve and effector/memory/exhausted CD8+ T (P14) cells were sorted by gating on CD8+ TCRVa2+ CD62L+ CD44lo and CD8+ TCRVa2+ CD45.2+ CD45.1- population, respectively. The following fluorochrome-conjugated antibodies from Biolegend were used for flow-cytometry: anti–TCR Vα2 (B20.1), anti-CD8α (53-6.7), anti-CD44 (IM7), anti-CD45.1 (A20), anti-CD45.2 (104), and anti-CD62L (MEL14). We sorted 40-50,000 cells per biological replicate (Naïve, Acute d8, Acute d27, Chronic d8, Chronic d27 and EL4), which were then washed once in cold PBS and lysed in 50μL cold lysis buffer (10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630). Lysed nuclei were incubated in Tn5 transposition reaction mix as described in (Buenrostro et al 2013) and purified using MinElute Reaction Cleanup kit (Qiagen). ATAC-seq fragments from one set of replicates for Acute d8, Acute d27, Chronic d8 and Chronic d27, as well as both biological replicates for Naïve cells and EL4 cells, were size selected for fragments between 115 and 600 bp using Pippin Prep 2% Agarose Gel Cassettes and the Pippin Prep DNA Size Selection System (Sage Science). Post size-selection, ATAC libraries were amplified and Nextera sequencing primers ligated using Polymerase Chain Reaction (PCR). Finally, PCR primers were removed using Agencourt AMPure XP bead cleanup (Beckman Coulter/Agencourt) and library quality was verified using a Tapestation machine. High quality ‘multiplexed’ DNA libraries were sequenced on the Illumina HiSeq2000. ATAC-Seq Illumina HiSeq 2000 gds 302337213 GEO Accession GSM2337213