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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T cells in SARS-CoV-2 infection and vaccination
TL;DR: Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed.
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The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA-supertype-dependent manner
TL;DR: This article analyzed a total of 330,246 high-quality SARS-CoV-2 genome assemblies, sampled across 143 countries and all major continents from December 2019 to December 2020 before mass vaccination or the rise of the Delta variant.
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The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner
David Hamelin,Dominique Fournelle,Jean-Christophe Grenier,Jana Schockaert,Kevin A. Kovalchik,Peter Kubiniok,Fatima Mostefai,Jerome Despault Duquette,Frederic Saab,Isabelle Sirois,Martin A. Smith,Sofie Pattijn,Hugo Soudeyns,Hélène Decaluwe,Julie Hussin,Julie Hussin,Etienne Caron +16 more
TL;DR: The authors analyzed a total of 330,246 high-quality SARS-CoV-2 genome assemblies, sampled across 143 countries and all major continents from December 2019 to December 2020 before mass vaccination or the rise of the Delta variant.
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Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors
Daichao Wu,Alexander V. Kolesnikov,Rui Yin,Johnathan D. Guest,Ragul Gowthaman,Anton Shmelev,Yana Serdyuk,Dmitry V. Dianov,Grigory A. Efimov,Brian G. Pierce,Roy A. Mariuzza +10 more
TL;DR: In this article , the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ) were determined.
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Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination
Krystallenia A. Paniskaki,Moritz Anft,Toni Luise Meister,Corinna Marheinecke,Stephanie Pfaender,Sarah Skrzypczyk,Felix S. Seibert,Constantin J. Thieme,Margarethe Konik,Sebastian Dolff,Olympia E. Anastasiou,Bodo Holzer,Ulf Dittmer,Christine Queren,Lutz Fricke,Hana Rohn,Timm H. Westhoff,Oliver Witzke,Ulrik Stervbo,Toralf Roch,Nina Babel +20 more
TL;DR: There is a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines, due to the delayed development of alpha S-specific cellular and humoral immunity upon VBI.
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