1. SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses
- Author
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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, Fae, Ingrid, Wenda, Sabine, Traugott, Marianna, Walder, Gernot, Pickl, Winfried F, Thiel, Volker, Allerberger, Franz, Stockinger, Hannes, Puchhammer-Stöckl, Elisabeth, Weninger, Wolfgang, Fischer, Gottfried, Hoepler, Wolfgang, Pawelka, Erich, Zoufaly, Alexander, Valenta, Rudolf, Bock, Christoph, Paster, Wolfgang, Geyeregger, René, Farlik, Matthias, Halbritter, Florian, Huppa, Johannes B, Aberle, Judith H, and Bergthaler, Andreas
- Subjects
viruses ,570 Life sciences ,biology ,610 Medicine & health ,3. Good health - 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.