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

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

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

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Figure 6

Time-dependent evolution of SARS-CoV-2–specific CD8+ T cell response, inflammation, and humoral immune response.

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Time-dependent evolution of SARS-CoV-2–specific CD8+ T cell response, in...
(A) Correlation matrix showing the associations between frequencies and phenotypic markers of SARS-CoV-2–specific T cells and plasma markers and recovery time (days since PCR). Spearman correlation (blue: positive correlation, red: negative correlation). *P < 0.05, P values were adjusted for multiple testing using the Bonferroni method. (B) Scatterplots showing the correlations between marker expression on SARS-CoV-2–specific T cells and neutralizing antibody activity. Higher expression of markers associated with T cell differentiation was associated with a stronger neutralizing antibody activity. (C) Scatterplots showing the correlations between marker expression on SARS-CoV-2–specific T cells and recovery time. The expression of markers associated with late-stage differentiation correlated with the donors’ recovery time (days since last swab was PCR positive). Correlations were calculated with the Spearman’s rank order test. Red dots indicate high-prevalence response hits.