Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8 + T cell repertoire upon viral exposure
Abstract
Effective presentation of antigens by 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, multi-omic technology to generate the first unified ex vivo characterization of the CD8 + T cell response to SARS-CoV-2 across 4 major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCR α/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 results show that HLA variations influence pre-existing immunity to SARS-CoV-2 and shape the immune repertoire upon subsequent viral exposure.
One-Sentence Summary
We perform a unified, multi-omic characterization of the CD8 + T cell response to SARS-CoV-2, revealing pre-existing immunity conditioned by HLA genotype.
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