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

Kared, Hassen; Redd, Andrew D; Bloch, Evan M; Bonny, Tania S.; Sumatoh, Hermi; Kairi, Faris; Carbajo, Daniel; Abel, Brian; Newell, Evan W; Bettinotti, Maria P.; Benner, Sarah E.; Patel, Eshan U.; Littlefield, Kirsten; Laeyendecker, Oliver; Shoham, Shmuel; Sullivan, David; Casadevall, Arturo; Pekosz, Andrew; Nardin, Alessandra; Fehlings, Michael; Tobian, Aaron AR; Quinn, Thomas C

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.