1. Suboptimal SARS-CoV-2−specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype.
- Author
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Habel, Jennifer R., Nguyen, Thi H. O., van de Sandt, Carolien E., Juno, Jennifer A., Chaurasia, Priyanka, Wragg, Kathleen, Koutsakos, Marios, Hensen, Luca, Xiaoxiao Jia, Brendon Chu, Wuji Zhang, Hyon-Xhi Tan, Flanagan, Katie L., Doolan, Denise L., Torresi, Joseph, Weisan Chen, Wakim, Linda M., Cheng, Allen C., Doherty, Peter C., and Petersen, Jan
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T cells , *COVID-19 - Abstract
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 HLAA* 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 cellswere 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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