SARS-CoV-2 mutations in MHC-I epitopes identified by deep viral sequencing evade CTL responses through decreased peptide-MHC-I binding. 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.
【초록키워드】 SARS-CoV-2, Immunity, T cells, Sequencing, COVID-19 severity, peptide, SARS-CoV-2 virus, in vitro, virus, CD8, Epitopes, T cell, Viral, Surveillance, response, RNA sequencing, peptides, point mutations, SARS-CoV-2 mutations, mutant, SARS-CoV-2 mutation, T cell epitope, CTL, COVID-19 patients, IFN-γ, binding, Point mutation, Nonsynonymous mutations, deep sequencing, isolates, COVID-19 patient, T cell epitopes, proliferation, MHC-I, Ex vivo, transcriptional response, cytotoxic activity, MHC-I epitopes, tetramer, Cell, highlight, nonsynonymous mutation, exhibited, evade, implicated, abrogated, MHC-I epitope, 【제목키워드】 CD8, response, SARS-CoV-2 mutation, epitope, evade,