In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 6, No. 57 ( 2021-03-04)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abg6461
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2021
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