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

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Abstract

Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (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 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2–specific CD8+ T cell responses detected across 6 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 nonstructural 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.

Authors

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