SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals
Hassen Kared, … , Aaron A.R. Tobian, Thomas C. Quinn
Hassen Kared, … , Aaron A.R. Tobian, Thomas C. Quinn
Published January 11, 2021
Citation Information: J Clin Invest. 2021;131(5):e145476. https://doi.org/10.1172/JCI145476.
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Research Article COVID-19 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 4

SARS-CoV-2–specific CD8+ T cells display a unique phenotype and can be categorized into different subsets.

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SARS-CoV-2–specific CD8+ T cells display a unique phenotype and can be c...
(A) Heatmap summarizing the expression frequencies of all phenotypic markers analyzed among the total pool of SARS-CoV-2–specific and unrelated control antigen–specific CD8+ T cells detected in the same cross-sectional sample. The majority of SARS-CoV-2–specific T cells cluster differently from common virus-specific T cells. Antigen specificities and phenotypic markers were clustered using Pearson correlation coefficients as distance measure. (B) UMAP plot showing the clustering of all antigen-specific T cells by antigen category. SARS-CoV-2–specific CD8+ T cells occupy the lower region of the 2D map. Clustering is based on the expression of all phenotypic markers assessed. Each dot represents 1 hit. (C) Differentiation profiles of SARS-CoV-2–specific CD8+ T cells and common virus control antigen–specific T cells. Based on the expression of the markers below the bar diagrams, antigen-specific and total CD8+ T cells were categorized into distinct states of differentiation. SARS-CoV-2–specific T cells were enriched in SCM and TM2 cells. Control virus hits could be separated into distinct subsets dependent on the target epitope. *P < 0.1, **P < 0.01, ***P < 0.001, ****P < 0.0001. Wilcoxon rank sum test. SCM, stem cell memory cells; TM, transitional memory cells; TEMRA, terminal effector memory cells reexpressing CD45RA; EM, effector memory cells; CM, central memory cells.