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

被引：184

作者：

Kared, Hassen ^{[1
]}

Redd, Andrew D. ^{[2
,3
]}

Bloch, Evan M. ^{[4
]}

Bonny, Tania S. ^{[4
]}

Sumatoh, Hermi ^{[1
]}

Kairi, Faris ^{[1
]}

Carbajo, Daniel ^{[1
]}

Abel, Brian ^{[1
]}

Newell, Evan W. ^{[1
,5
]}

Bettinotti, Maria P. ^{[4
]}

Benner, Sarah E. ^{[4
]}

Patel, Eshan U. ^{[4
,6
]}

Littlefield, Kirsten ^{[7
]}

Laeyendecker, Oliver ^{[2
,3
]}

Shoham, Shmuel ^{[3
]}

Sullivan, David ^{[7
]}

Casadevall, Arturo ^{[7
]}

Pekosz, Andrew ^{[7
]}

Nardin, Alessandra ^{[1
]}

Fehlings, Michael ^{[1
]}

Tobian, Aaron A. R. ^{[4
]}

Quinn, Thomas C. ^{[2
,3
]}

机构：

[1] ImmunoScape, Singapore, Singapore

[2] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[5] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[6] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[7] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2021年 / 131卷 / 05期

关键词：

D O I：

10.1172/JCI145476

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 CO8(+) 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.

引用

页数：14

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