SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes

Agerer, B.; Koblischke, M.; Gudipati, V.; Smyth, M.; Popa, A.; Genger, J.-W.; Endler, L.; Florian, D. M.; Muehlgrabner, V.; Lercher, A.; Gattinger, P.; Torralba-Gombau, R.; Penz, T.; Fae, I.; Wenda, S.; Traungott, M.; Walder, G.; Fischer, G.; Hoepler, W.; Pawelka, E.; Zoufaly, A.; Valenta, R.; Bock, C.; Huppa, J. B.; Aberle, J. H.; Bergthaler, A.

doi:10.1101/2020.12.18.423507

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bioRxiv · 10.1101/2020.12.18.423507

SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes

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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.

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Agerer, B., Koblischke, M., Gudipati, V., Smyth, M., Popa, A., Genger, J.-W., Endler, L., Florian, D. M., Muehlgrabner, V., Lercher, A., Gattinger, P., Torralba-Gombau, R., Penz, T., Fae, I., Wenda, S., Traungott, M., Walder, G., Fischer, G., Hoepler, W., Pawelka, E., Zoufaly, A., Valenta, R., Bock, C., Huppa, J. B., Aberle, J. H., Bergthaler, A.. 2020-12-20. SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes. https://doi.org/10.1101/2020.12.18.423507

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