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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Differences in Presentation of SARS-CoV-2 Omicron Strain Variant BA.1–BA.5 Peptides by HLA Molecules
TL;DR: In this article , the binding affinities of mutated peptides of Omicron strain variants BA.1-BA.5 and the worldwide prevalent HLA alleles were analyzed with the use of T-CoV web portal.
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In Silico Defined SARS-CoV2 Epitopes May Not Predict Immunogenicity to COVID19
Ke Pan,Yulun Chiu,Mei-Ju May Chen,Junmei Wang,Ivy Lai,Shubhra Singh,Richard Shaw,Cassian Yee +7 more
TL;DR: In this paper, the authors find that immunogenic peptides defined by such in-silico methods often fail to elicit T cell responses recognizing naturally presented SARS-CoV-2 epitopes.
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Highly Networked SARS-CoV-2 Peptides Elicit T Cell Responses with Enhanced Specificity.
Gabriel Duette,Eunok Lee,Gabriela Martins Costa Gomes,Katie Tungatt,Chloe M Doyle,Vicki V. Stylianou,Ashley Lee,Susan Maddocks,Janette Taylor,Rajiv Khanna,Rowena A. Bull,Marianne Martinello,Kerrie J. Sandgren,Anthony L. Cunningham,Sarah Palmer +14 more
TL;DR: In this paper , the authors identified SARS-CoV-2-specific peptides within topologically and structurally essential regions of SARS CoV2 spike and nucleocapsid proteins by applying an immunoinformatics pipeline.
Posted ContentDOI
Structural basis for recognition of two HLA-A2-restricted SARS-CoV-2 spike epitopes by public and private T cell receptors
Daichao Wu,Daichao Wu,Alexander Kolesnikov,Rui Yin,Johnathan D. Guest,Ragul Gowthaman,Anton Shmelev,Yana Serdyuk,Grigory A. Efimov,Brian G. Pierce,Roy A. Mariuzza +10 more
TL;DR: The structures revealed the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of both TCRs to recognize natural variants of YLQ and RLQ but not homologous epitopes from human seasonal coronaviruses.
Journal ArticleDOI
Architecture of the SARS-CoV-2-specific T cell repertoire
TL;DR: The role of cellular immunity in the early control and successful clearance of SARS-CoV-2 infection and the subsequent course of disease is discussed in this article , including the shape and composition of disease-specific T cell repertoires across convalescent patients and vaccinated individuals.
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