Benedikt Agerer1, Maximilian Koblischke2, Venugopal Gudipati3, Luis Fernando Montaño-Gutierrez4, Mark Smyth1, Alexandra Popa1, Jakob-Wendelin Genger1, Lukas Endler1, David M Florian2, Vanessa Mühlgrabner3, Marianne Graninger2, Stephan W Aberle2, Anna-Maria Husa4, Lisa Ellen Shaw5, Alexander Lercher1, Pia Gattinger6, Ricard Torralba-Gombau1, Doris Trapin7, Thomas Penz1, Daniele Barreca1, Ingrid Fae8, Sabine Wenda8, Marianna Traugott9, Gernot Walder10, Winfried F Pickl711, Volker Thiel1213, Franz Allerberger14, Hannes Stockinger3, Elisabeth Puchhammer-Stöckl2, Wolfgang Weninger5, Gottfried Fischer7, Wolfgang Hoepler9, Erich Pawelka8, Alexander Zoufaly8, Rudolf Valenta36111516, Christoph Bock117, Wolfgang Paster4, René Geyeregger4, Matthias Farlik5, Florian Halbritter4, Johannes B Huppa3, Judith H Aberle2, Andreas Bergthaler18
Sci Immunol. 2021 Mar 4;6(57):eabg6461. doi: 10.1126/sciimmunol.abg6461.
AbstractCD8+ 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.
Links: PMID: 33664060; DOI: 10.1126/sciimmunol.abg6461