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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
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, Volume 117, No. 39, Year 2020
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Description
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/ S269-277 and A2/Orf1ab3183-3191. Using peptide−HLA tetramer enrichment, direct ex vivo assessment of A2/S269+CD8+ and A2/ Orf1ab3183+CD8+ populations indicated that A2/S269+CD8+ T cells were detected at comparable frequencies (∼1.3 × 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 (∼2.5 × 10−6), but low when compared to frequencies for influenza-specific (A2/M158) and Epstein-Barr virus (EBV)-specific (A2/BMLF1280) (∼1.38 × 10−4) populations. Phenotyping A2/S269+CD8+ T cells from COVID-19 convalescents ex vivo showed that A2/S269+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 naïve, stem cell memory and central memory A2/S269+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. © 2020 National Academy of Sciences. All rights reserved.
Authors & Co-Authors
Nguyen, Thi H.O.
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Juno, Jennifer A.
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Koutsakos, Marios
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Flanagan, Katie L.
Australia, Launceston
Launceston General Hospital
Australia, Hobart
University of Tasmania
Australia, Clayton
Monash University
Australia, Melbourne
Rmit University
Doolan, Denise L.
Australia, Townsville
James Cook University
Torresi, Joseph
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Cheng, Allen C.
Australia, Clayton
Monash University
Rossjohn, Jamie
Australia, Clayton
Monash University
United Kingdom, Cardiff
Cardiff University
Wheatley, Adam Kenneth
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Australia, Melbourne
University of Melbourne
Kent, Stephen J.
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Australia, Melbourne
University of Melbourne
Kedzierska, Katherine
Australia, Melbourne
The Peter Doherty Institute for Infection and Immunity
Statistics
Citations: 127
Authors: 11
Affiliations: 11
Identifiers
Doi:
10.1073/pnas.2015486117
ISSN:
00278424
Research Areas
Covid