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Sci Immunol ; 6(57)2021 03 04.
Article in English | MEDLINE | ID: covidwho-1148101


CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding in a cell-free in vitro assay. Reduced MHC-I binding of mutant peptides was associated with decreased proliferation, IFN-γ production and cytotoxic activity of CD8+ T cells isolated from HLA-matched COVID-19 patients. Single cell RNA sequencing of ex vivo expanded, tetramer-sorted CD8+ T cells from COVID-19 patients further revealed qualitative differences in the transcriptional response to mutant peptides. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.

CD8-Positive T-Lymphocytes/immunology , COVID-19 , Epitopes, T-Lymphocyte , HLA-A Antigens/immunology , Immunity, Cellular , Mutation , SARS-CoV-2 , CD8-Positive T-Lymphocytes/pathology , COVID-19/genetics , COVID-19/immunology , COVID-19/pathology , Cell Proliferation , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , High-Throughput Nucleotide Sequencing , Humans , Interferon-gamma/immunology , Peptides/genetics , Peptides/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology