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Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with the prominent HLA-A*02:01 phenotype


Habel, JR and Nguyen, THO and van de Sandt, CE and Juno, JA and Chaurasia, P and Wragg, K and Koutsakos, M and Hensen, L and Jia, XX and Chua, B and Zhang, WJ and Tan, HX and Flanagan, KL and Doolan, DL and Torresi, J and Chen, W and Wakim, LM and Cheng, AC and Doherty, PC and Petersen, J and Rossjohn, J and Wheatley, AK and Kent, SJ and Rowntree, LC and Kedzierska, K, Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with the prominent HLA-A*02:01 phenotype, Proceedings of the National Academy of Sciences of the United States of America, 117, (39) pp. 24384-24391. ISSN 0027-8424 (2020) [Refereed Article]

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Copyright Statement

2020 the Author(s). Published by PNAS This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, (

DOI: doi:10.1073/pnas.2015486117


An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8(+) T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8(+) and CD4(+) T cells in vitro, with CD4(+) T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8(+) T cell epitopes, A2/S-269(-2)77 and A2/Orf1ab(3183-3191). Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S(269)(+)CD8(+) and A2/Orf1ab(3183)(+)CD8(+) populations indicated that A2/S(269)(+)CD8(+ )T cells were detected at comparable frequencies (similar to 1.3 x 10(-5)) in acute and convalescent HLA-A*02:01(+) patients. These frequencies were higher than those found in uninfected HLA-A*02:01(+) donors (similar to 2.5 x 10(-6)), but low when compared to frequencies for influenza-specific (A2/M1(58)) and Epstein-Barr virus (EBV)-specific (A2/BMLF1280) (similar to 1.38 x 10(-4)) populations. Phenotyping A2/S(269)(+)CD8(+) T cells from COVID-19 convalescents ex vivo showed that A2/S(269)(+)CD8(+) T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8(+) T cells expressed granzymes and/or perforin. Furthermore, the bias toward naive, stem cell memory and central memory A2/S(269)(+)CD8(+) T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8(+) T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8(+) T cell immunity in COVID-19.

Item Details

Item Type:Refereed Article
Keywords:CD8+T cells; COVID-19; HLA-A*02:01; SARS-CoV-2 epitopes
Research Division:Health Sciences
Research Group:Other health sciences
Research Field:Other health sciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Efficacy of medications
UTAS Author:Flanagan, KL (Dr Katie Flanagan)
ID Code:152913
Year Published:2020
Web of Science® Times Cited:88
Deposited By:Physics
Deposited On:2022-08-26
Last Modified:2022-11-09
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