SARS-CoV-2-specific CD8+ T cell responses in convalescent COVID-19 individuals.

Kared, Hassen; Redd, Andrew D; Bloch, Evan M; Bonny, Tania S; Sumatoh, Hermi R; Kairi, Faris; Carbajo, Daniel; Abel, Brian; Newell, Evan W; Bettinotti, Maria; 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 understand 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. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across six different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and non-structural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. 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.