SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses.

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; ... (2021). SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses. Science immunology, 6(57) American Association for the Advancement of Science 10.1126/sciimmunol.abg6461

Text b156603.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (1MB)

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.

Interest & Impact

Downloads

1 since deposited on 13 Jul 2021
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item