%0 Journal Article %A Felix Schreibing %A Monica Hannani %A Fabio Ticconi %A Eleanor Fewings %A James S Nagai %A Matthias Begemann %A Christoph Kuppe %A Ingo Kurth %A Jennifer Kranz %A Dario Frank %A Teresa M Anslinger %A Patrick Ziegler %A Thomas Kraus %A Jürgen Enczmann %A Vera Balz %A Frank Windhofer %A Paul Balfanz %A Christian Kurts %A Gernot Marx %A Nikolaus Marx %A Michael Dreher %A Rebekka K Schneider %A Julio Saez-Rodriguez %A Ivan Costa %A Rafael Kramann %T Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping %D 2021 %R 10.1101/2021.03.03.432690 %J bioRxiv %P 2021.03.03.432690 %X 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 StatementThe authors have no competing interests. Julio Saez-Rodriguez declares funding from GSK and Sanofi and consultant fees from Travere Therapeutics unrelated to this study. %U https://www.biorxiv.org/content/biorxiv/early/2021/03/03/2021.03.03.432690.full.pdf