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Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping

View ORCID ProfileFelix Schreibing, View ORCID ProfileMonica Hannani, View ORCID ProfileFabio Ticconi, View ORCID ProfileEleanor Fewings, View ORCID ProfileJames S Nagai, View ORCID ProfileMatthias Begemann, View ORCID ProfileChristoph Kuppe, View ORCID ProfileIngo Kurth, View ORCID ProfileJennifer Kranz, Dario Frank, View ORCID ProfileTeresa M Anslinger, Patrick Ziegler, Thomas Kraus, Jürgen Enczmann, Vera Balz, Frank Windhofer, Paul Balfanz, Christian Kurts, Gernot Marx, Nikolaus Marx, Michael Dreher, View ORCID ProfileRebekka K Schneider, View ORCID ProfileJulio Saez-Rodriguez, View ORCID ProfileIvan Costa, View ORCID ProfileRafael Kramann
doi: https://doi.org/10.1101/2021.03.03.432690
Felix Schreibing
1Institute of Experimental Medicine and Systems Biology, University Hospital RWTH Aachen, Germany
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Monica Hannani
1Institute of Experimental Medicine and Systems Biology, University Hospital RWTH Aachen, Germany
2Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany
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Fabio Ticconi
3Institute for Computational Genomics, University Hospital RWTH Aachen
4Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen
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Eleanor Fewings
2Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany
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James S Nagai
3Institute for Computational Genomics, University Hospital RWTH Aachen
4Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen
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Matthias Begemann
5Institute of Human Genetics, Medical Faculty, RWTH Aachen University Hospital, Aachen, Germany
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Christoph Kuppe
1Institute of Experimental Medicine and Systems Biology, University Hospital RWTH Aachen, Germany
6Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), University Hospital RWTH Aachen
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Ingo Kurth
5Institute of Human Genetics, Medical Faculty, RWTH Aachen University Hospital, Aachen, Germany
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  • ORCID record for Ingo Kurth
Jennifer Kranz
1Institute of Experimental Medicine and Systems Biology, University Hospital RWTH Aachen, Germany
7Department of Urology and Paediatric Urology, St Antonius Hospital, Eschweiler, Germany
8Department of Urology and Kidney Transplantation, Martin Luther University, Halle (Saale), Germany
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Dario Frank
9Department of Medicine, St Antonius Hospital, Eschweiler, Germany
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Teresa M Anslinger
6Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), University Hospital RWTH Aachen
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Patrick Ziegler
10Institute for Occupational, Social and Environmental Medicine, University Hospital RWTH Aachen
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Thomas Kraus
10Institute for Occupational, Social and Environmental Medicine, University Hospital RWTH Aachen
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Jürgen Enczmann
11Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Düsseldorf, Germany
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Vera Balz
11Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Düsseldorf, Germany
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Frank Windhofer
11Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, Düsseldorf, Germany
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Paul Balfanz
12Department of Cardiology, Angiology and Intensive Care Medicine, University Hospital RWTH Aachen
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Christian Kurts
13Institute of Experimental Immunology, University of Bonn, Germany
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Gernot Marx
14Department of Intensive and Intermediate Care, University Hospital RWTH Aachen
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Nikolaus Marx
12Department of Cardiology, Angiology and Intensive Care Medicine, University Hospital RWTH Aachen
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Michael Dreher
15Department of Pneumology and Intensive Care Medicine, University Hospital RWTH Aachen
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Rebekka K Schneider
16Department of Cell Biology, RWTH Aachen University
17Department of Developmental Biology, Erasmus Medical Center, Rotterdam, The Netherlands
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Julio Saez-Rodriguez
2Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany
4Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen
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Ivan Costa
3Institute for Computational Genomics, University Hospital RWTH Aachen
4Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen
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Rafael Kramann
1Institute of Experimental Medicine and Systems Biology, University Hospital RWTH Aachen, Germany
6Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), University Hospital RWTH Aachen
18Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
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  • For correspondence: rkramann@gmx.net
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Abstract

The current COVID-19 pandemic represents a global challenge. A better understanding of the immune response against SARS-CoV-2 is key to unveil the differences in disease severity and to develop future vaccines targeting novel SARS-CoV-2 variants. Feature barcode technology combined with CITE-seq antibodies and DNA-barcoded peptide-MHC I Dextramer reagents enabled us to identify relevant SARS-CoV-2-derived epitopes and compare epitope-specific CD8+ T cell populations between mild and severe COVID-19. We identified a strong CD8+ T cell response against an S protein-derived epitope. CD8+ effector cells in severe COVID-19 displayed hyperactivation, T cell exhaustion and were missing characteristics of long-lived memory T cells. We identify A*0101 WTAGAAAYY as an immunogenic CD8+ T cell epitope with the ability to drive clonal expansion. We provide an in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection which will be relevant for the development of molecular and targeted therapies and potential adjustments of vaccination strategies.

Competing Interest Statement

The authors have no competing interests. Julio Saez-Rodriguez declares funding from GSK and Sanofi and consultant fees from Travere Therapeutics unrelated to this study.

Footnotes

  • ↵† Co-first/senior authors

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-ND 4.0 International license.
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Posted March 03, 2021.
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Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping
Felix Schreibing, Monica Hannani, Fabio Ticconi, Eleanor Fewings, James S Nagai, Matthias Begemann, Christoph Kuppe, Ingo Kurth, Jennifer Kranz, Dario Frank, Teresa M Anslinger, Patrick Ziegler, Thomas Kraus, Jürgen Enczmann, Vera Balz, Frank Windhofer, Paul Balfanz, Christian Kurts, Gernot Marx, Nikolaus Marx, Michael Dreher, Rebekka K Schneider, Julio Saez-Rodriguez, Ivan Costa, Rafael Kramann
bioRxiv 2021.03.03.432690; doi: https://doi.org/10.1101/2021.03.03.432690
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Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping
Felix Schreibing, Monica Hannani, Fabio Ticconi, Eleanor Fewings, James S Nagai, Matthias Begemann, Christoph Kuppe, Ingo Kurth, Jennifer Kranz, Dario Frank, Teresa M Anslinger, Patrick Ziegler, Thomas Kraus, Jürgen Enczmann, Vera Balz, Frank Windhofer, Paul Balfanz, Christian Kurts, Gernot Marx, Nikolaus Marx, Michael Dreher, Rebekka K Schneider, Julio Saez-Rodriguez, Ivan Costa, Rafael Kramann
bioRxiv 2021.03.03.432690; doi: https://doi.org/10.1101/2021.03.03.432690

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