Allelic variation in class I HLA determines CD8⁺ T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2.

ABSTRACT: 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, TCRα/β 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 r

SUBMITTER: Francis JM 

PROVIDER: S-EPMC9017864 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature