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

Schreibing, F.; Hannani, M.; Ticconi, F.; Fewings, E.; Nagai, J. S.; Begemann, M.; Kuppe, C.; Kurth, I.; Kranz, J.; Frank, D.; Anslinger, T. M.; Ziegler, P.; Kraus, T.; Enczmann, J.; Balz, V.; Windhofer, F.; Balfanz, P.; Kurts, C.; Marx, G.; Marx, N.; Dreher, M.; Schneider, R. K.; Saez-Rodriguez, J.; Costa Filho, I. G.; Kramann, R.

doi:10.1101/2021.03.03.432690

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bioRxiv · 10.1101/2021.03.03.432690

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

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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.

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Schreibing, F., Hannani, M., Ticconi, F., Fewings, E., Nagai, J. S., Begemann, M., Kuppe, C., Kurth, I., Kranz, J., Frank, D., Anslinger, T. M., Ziegler, P., Kraus, T., Enczmann, J., Balz, V., Windhofer, F., Balfanz, P., Kurts, C., Marx, G., Marx, N., Dreher, M., Schneider, R. K., Saez-Rodriguez, J., Costa Filho, I. G., Kramann, R.. 2021-03-03. Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping. https://doi.org/10.1101/2021.03.03.432690

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