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- Title
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8<sup>+</sup> T cell responses.
- Authors
Agerer, Benedikt; Koblischke, Maximilian; Gudipati, Venugopal; Montaño-Gutierrez, Luis Fernando; Smyth, Mark; Popa, Alexandra; Genger, Jakob-Wendelin; Endler, Lukas; Florian, David M.; Mühlgrabner, Vanessa; Graninger, Marianne; Aberle, Stephan W.; Husa, Anna-Maria; Shaw, Lisa Ellen; Lercher, Alexander; Gattinger, Pia; Torralba-Gombau, Ricard; Trapin, Doris; Penz, Thomas; Barreca, Daniele
- 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.
- Publication
Science Immunology, 2021, Vol 6, Issue 57, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abg6461