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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 Mühlgrabner, 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, View ORCID ProfileChristoph Bock, Johannes B. Huppa, Judith H. Aberle, View ORCID ProfileAndreas Bergthaler
doi: https://doi.org/10.1101/2020.12.18.423507
Benedikt Agerer
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Maximilian Koblischke
2Center for Virology, Medical University of Vienna, Vienna, Austria
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Venugopal Gudipati
3Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Mark Smyth
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Alexandra Popa
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Jakob-Wendelin Genger
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Lukas Endler
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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David M. Florian
2Center for Virology, Medical University of Vienna, Vienna, Austria
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Vanessa Mühlgrabner
3Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Alexander Lercher
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Pia Gattinger
4Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Ricard Torralba-Gombau
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Thomas Penz
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Ingrid Fae
5Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
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Sabine Wenda
5Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
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Marianna Traungott
6Department of Medicine IV, Kaiser Franz Josef Hospital, Vienna, Austria
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Gernot Walder
7Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
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Gottfried Fischer
5Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
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Wolfgang Hoepler
6Department of Medicine IV, Kaiser Franz Josef Hospital, Vienna, Austria
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Erich Pawelka
6Department of Medicine IV, Kaiser Franz Josef Hospital, Vienna, Austria
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Alexander Zoufaly
6Department of Medicine IV, Kaiser Franz Josef Hospital, Vienna, Austria
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Rudolf Valenta
4Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Christoph Bock
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
8Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
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  • ORCID record for Christoph Bock
Johannes B. Huppa
3Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Judith H. Aberle
2Center for Virology, Medical University of Vienna, Vienna, Austria
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Andreas Bergthaler
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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  • ORCID record for Andreas Bergthaler
  • For correspondence: abergthaler@cemm.oeaw.ac.at
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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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 20, 2020.
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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 Mühlgrabner, 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
bioRxiv 2020.12.18.423507; doi: https://doi.org/10.1101/2020.12.18.423507
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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 Mühlgrabner, 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
bioRxiv 2020.12.18.423507; doi: https://doi.org/10.1101/2020.12.18.423507

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