SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8 + T cell responses.
Benedikt Agerer,Maximilian Koblischke,Venugopal Gudipati,Luis F Montano-Gutierrez,Mark J. Smyth,Alexandra Popa,Jakob-Wendelin Genger,Lukas Endler,David M. Florian,Vanessa Mühlgrabner,Marianne Graninger,Stephan W. Aberle,Anna-Maria Husa,Lisa Ellen Shaw,Alexander Lercher,Pia Gattinger,Ricard Torralba-Gombau,Doris Trapin,Thomas Penz,Daniele Barreca,Ingrid Fae,S. Wenda,Marianna Traugott,Gernot Walder,Winfried F. Pickl,Winfried F. Pickl,Volker Thiel,Franz Allerberger,Hannes Stockinger,Elisabeth Puchhammer-Stöckl,Wolfgang Weninger,Gottfried Fischer,Wolfgang Hoepler,Erich Pawelka,Alexander Zoufaly,Rudolf Valenta,Christoph Bock,Christoph Bock,Wolfgang Paster,René Geyeregger,Matthias Farlik,Florian Halbritter,Johannes B. Huppa,Judith H. Aberle,Andreas Bergthaler +44 more
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TLDR
In this paper, nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes were identified after deep sequencing of 747 SARS-CoV-2 virus isolates.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.read more
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The biological and clinical significance of emerging SARS-CoV-2 variants.
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CD8 + T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients.
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TL;DR: In this paper, the authors used x-ray crystallography and cryo-electron microscopy to define two distinct binding epitopes of the SARS-CoV-2 spike protein.
Journal ArticleDOI
Unbiased Screens Show CD8 + T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.
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TL;DR: An unbiased, genome-wide screening technology was used to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients, and found that CD8- T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold.
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