PMID- 34793243 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20230801 IS - 2470-9468 (Electronic) IS - 2470-9468 (Linking) VI - 7 IP - 67 DP - 2022 Jan 21 TI - Allelic variation in class I HLA determines CD8(+) T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2. PG - eabk3070 LID - 10.1126/sciimmunol.abk3070 [doi] LID - eabk3070 AB - Effective presentation of antigens by human leukocyte antigen (HLA) class I molecules to CD8(+) T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multiomic technology to generate a unified ex vivo characterization of the CD8(+) T cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across four major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCRalpha/beta sequence diversity, and the utilization of pre-existing SARS-CoV-2-reactive memory T cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations notably influence the CD8(+) T cell repertoire shape and utilization of immune recall upon SARS-CoV-2 infection. FAU - Francis, Joshua M AU - Francis JM AUID- ORCID: 0000-0001-5727-7498 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Leistritz-Edwards, Del AU - Leistritz-Edwards D AUID- ORCID: 0000-0002-5286-6573 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Dunn, Augustine AU - Dunn A AUID- ORCID: 0000-0002-8683-1459 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Tarr, Christina AU - Tarr C AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Lehman, Jesse AU - Lehman J AUID- ORCID: 0000-0002-3729-2866 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Dempsey, Conor AU - Dempsey C AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Hamel, Andrew AU - Hamel A AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Rayon, Violeta AU - Rayon V AUID- ORCID: 0000-0002-2446-2395 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Liu, Gang AU - Liu G AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Wang, Yuntong AU - Wang Y AUID- ORCID: 0000-0001-9331-2959 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Wille, Marcos AU - Wille M AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Durkin, Melissa AU - Durkin M AUID- ORCID: 0000-0001-6886-2203 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Hadley, Kane AU - Hadley K AUID- ORCID: 0000-0002-2520-155X AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Sheena, Aswathy AU - Sheena A AUID- ORCID: 0000-0002-7277-457X AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Roscoe, Benjamin AU - Roscoe B AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Ng, Mark AU - Ng M AUID- ORCID: 0000-0002-3289-135X AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Rockwell, Graham AU - Rockwell G AUID- ORCID: 0000-0003-2738-326X AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Manto, Margaret AU - Manto M AUID- ORCID: 0000-0002-9393-179X AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Gienger, Elizabeth AU - Gienger E AUID- ORCID: 0000-0001-7647-1229 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Nickerson, Joshua AU - Nickerson J AUID- ORCID: 0000-0001-5125-229X AD - Repertoire Immune Medicines, Cambridge, MA, USA. CN - MGH COVID-19 Collection and Processing Team AD - Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Moarefi, Amir AU - Moarefi A AUID- ORCID: 0000-0002-3047-8262 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Noble, Michael AU - Noble M AUID- ORCID: 0000-0002-6704-1793 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Malia, Thomas AU - Malia T AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Bardwell, Philip D AU - Bardwell PD AUID- ORCID: 0000-0002-3835-255X AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Gordon, William AU - Gordon W AUID- ORCID: 0000-0003-2032-2325 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Swain, Joanna AU - Swain J AUID- ORCID: 0000-0003-0818-8434 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Skoberne, Mojca AU - Skoberne M AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Sauer, Karsten AU - Sauer K AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Harris, Tim AU - Harris T AUID- ORCID: 0000-0002-5621-7861 AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Goldrath, Ananda W AU - Goldrath AW AUID- ORCID: 0000-0002-5900-508X AD - Division of Biological Sciences, Molecular Biology Section, University of California, San Diego, San Diego, CA, USA. FAU - Shalek, Alex K AU - Shalek AK AUID- ORCID: 0000-0001-5670-8778 AD - Repertoire Immune Medicines, Cambridge, MA, USA. AD - Department of Chemistry and Koch Institute for Integrative Cancer Research, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. AD - Broad Institute of MIT and Harvard, Cambridge, MA, USA. AD - Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. FAU - Coyle, Anthony J AU - Coyle AJ AD - Repertoire Immune Medicines, Cambridge, MA, USA. FAU - Benoist, Christophe AU - Benoist C AUID- ORCID: 0000-0003-1172-6555 AD - Department of Immunology, Harvard Medical School, Boston, MA, USA. FAU - Pregibon, Daniel C AU - Pregibon DC AUID- ORCID: 0000-0003-1084-3653 AD - Repertoire Immune Medicines, Cambridge, MA, USA. LA - eng GR - R37 AI067545/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220121 PL - United States TA - Sci Immunol JT - Science immunology JID - 101688624 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) SB - IM MH - *Alleles MH - CD8-Positive T-Lymphocytes/*immunology MH - *COVID-19/genetics/immunology MH - Histocompatibility Antigens Class I/genetics/*immunology MH - Humans MH - Memory T Cells/*immunology MH - *Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology MH - SARS-CoV-2/genetics/*immunology PMC - PMC9017864 EDAT- 2021/11/19 06:00 MHDA- 2022/02/03 06:00 PMCR- 2021/11/18 CRDT- 2021/11/18 17:13 PHST- 2021/11/19 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] PHST- 2021/11/18 17:13 [entrez] PHST- 2021/11/18 00:00 [pmc-release] AID - 10.1126/sciimmunol.abk3070 [pii] AID - abk3070 [pii] AID - 10.1126/sciimmunol.abk3070 [doi] PST - ppublish SO - Sci Immunol. 2022 Jan 21;7(67):eabk3070. doi: 10.1126/sciimmunol.abk3070. Epub 2022 Jan 21.