Suboptimal SARS-CoV-2−specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype Academic Article uri icon

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 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.

authors

  • Habel, Jennifer R
  • Nguyen, Thi HO
  • van de Sandt, Carolien E
  • Juno, Jennifer A
  • Chaurasia, Priyanka
  • Wragg, Kathleen
  • Koutsakos, Marios
  • Hensen, Luca
  • Jia, Xiaoxiao
  • Chua, Brendon
  • Zhang, Wuji
  • Tan, Hyon-Xhi
  • Flanagan, Katie L
  • Doolan, Denise L
  • Torresi, Joseph
  • Chen, Weisan
  • Wakim, Linda M
  • Cheng, Allen C
  • Doherty, Peter C
  • Petersen, Jan
  • Rossjohn, Jamie
  • Wheatley, Adam K
  • Kent, Stephen J
  • Rowntree, Louise C
  • Kedzierska, Katherine

publication date

  • 2020