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

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Habel, JR; Nguyen, THO; van de Sandt, CE; Juno, JA; Chaurasia, P; Wragg, K; Koutsakos, M; Hensen, L; Jia, X; Chua, B; ...Date
2020-09-29Source Title
Proceedings of the National Academy of Sciences of USAPublisher
NATL ACAD SCIENCESUniversity of Melbourne Author/s
Chua, Brendon; Kent, Stephen; Kedzierska, Katherine; Wheatley, Adam; Nguyen, Thi Hoang Oanh; Tan, Hyon Xhi; Juno, Jennifer; Van de Sandt, Carolien; Rowntree, Louise; Wakim, Linda; ...Affiliation
Microbiology and ImmunologyMetadata
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Habel, J. R., Nguyen, T. H. O., van de Sandt, C. E., Juno, J. A., Chaurasia, P., Wragg, K., Koutsakos, M., Hensen, L., Jia, X., Chua, B., Zhang, W., Tan, H. -X., Flanagan, K. L., Doolan, D. L., Torresi, J., Chen, W., Wakim, L. M., Cheng, A. C., Doherty, P. C. ,... Kedzierska, K. (2020). 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. https://doi.org/10.1073/pnas.2015486117.Access Status
Open AccessAbstract
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.
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