CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entireSARS-CoV-2 proteome and show kinetics of early differentiation

Kared, H.; Redd, A. D.; Bloch, E. M.; Bonny, T. S.; Sumatoh, H.; Kairi, F.; Carbajo, D.; Abel, B.; Newell, E. W.; Bettinotti, M. P.; Benner, S. E.; Patel, E. U.; Littlefield, K.; Laeyendecker, O.; Shoham, S.; Sullivan, D.; Casadevall, A.; Pekosz, A.; Nardin, A.; Fehlings, M.; Tobian, A. A.; Quinn, T. C.

doi:10.1101/2020.10.08.330688

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bioRxiv · 10.1101/2020.10.08.330688

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entireSARS-CoV-2 proteome and show kinetics of early differentiation

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Abstract

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

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Kared, H., Redd, A. D., Bloch, E. M., Bonny, T. S., Sumatoh, H., Kairi, F., Carbajo, D., Abel, B., Newell, E. W., Bettinotti, M. P., Benner, S. E., Patel, E. U., Littlefield, K., Laeyendecker, O., Shoham, S., Sullivan, D., Casadevall, A., Pekosz, A., Nardin, A., Fehlings, M., Tobian, A. A., Quinn, T. C.. 2020-10-08. CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entireSARS-CoV-2 proteome and show kinetics of early differentiation. https://doi.org/10.1101/2020.10.08.330688

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