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SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes
Benedikt Agerer; Maximilian Koblischke; Venugopal Gudipati; Mark Smyth; Alexandra Popa; Jakob-Wendelin Genger; Lukas Endler; David M Florian; Vanessa Muehlgrabner; Alexander Lercher; Pia Gattinger; Ricard Torralba-Gombau; Thomas Penz; Ingrid Fae; Sabine Wenda; Marianna Traungott; Gernot Walder; Gottfried Fischer; Wolfgang Hoepler; Erich Pawelka; Alexander Zoufaly; Rudolf Valenta; Christoph Bock; Johannes B. Huppa; Judith H. Aberle; Andreas Bergthaler.
Afiliação
  • Benedikt Agerer; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Maximilian Koblischke; Center for Virology, Medical University of Vienna
  • Venugopal Gudipati; Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna
  • Mark Smyth; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Alexandra Popa; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Jakob-Wendelin Genger; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Lukas Endler; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • David M Florian; Center for Virology, Medical University of Vienna
  • Vanessa Muehlgrabner; Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna
  • Alexander Lercher; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Pia Gattinger; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna
  • Ricard Torralba-Gombau; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Thomas Penz; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Ingrid Fae; Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna
  • Sabine Wenda; Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna
  • Marianna Traungott; Department of Medicine IV, Kaiser Franz Josef Hospital
  • Gernot Walder; Division of Hygiene and Medical Microbiology, Medical University of Innsbruck
  • Gottfried Fischer; Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna
  • Wolfgang Hoepler; Department of Medicine IV, Kaiser Franz Josef Hospital
  • Erich Pawelka; Department of Medicine IV, Kaiser Franz Josef Hospital
  • Alexander Zoufaly; Department of Medicine IV, Kaiser Franz Josef Hospital
  • Rudolf Valenta; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna
  • Christoph Bock; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
  • Johannes B. Huppa; Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna
  • Judith H. Aberle; Center for Virology, Medical University of Vienna
  • Andreas Bergthaler; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-423507
ABSTRACT
CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control, though direct evidence has been lacking so far. Here, we identified non-synonymous 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, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through escape mutations in MHCI-restricted viral epitopes. This provides evolutionary evidence for CD8+ T cell immunity controlling SARS-CoV-2 with consequences for COVID-19 vaccine design.
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Estudo prognóstico Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Estudo prognóstico Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
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