Suboptimal SARS-CoV-2−specific CD8 <sup>+</sup> T cell response associated with the prominent HLA-A*02:01 phenotype
Jennifer R. Habel, Thi H. O. Nguyen, Carolien E. van de Sandt, Jennifer A. Juno, Priyanka Chaurasia, Kathleen M. Wragg, Marios Koutsakos, Luca Hensen, Xiaoxiao Jia, Brendon Y. Chua, Wuji Zhang, Hyon‐Xhi Tan, Katie L. Flanagan, Denise L. Doolan, Joseph Torresi, Weisan Chen, Linda M. Wakim, Allen Cheng, Peter C. Doherty, Jan Petersen, Jamie Rossjohn, Adam K. Wheatley, Stephen J. Kent, Louise C. Rowntree, Katherine Kedzierska
Abstract
Significance As the recall of CD8 + T cell memory promotes rapid recovery in, for example, influenza, we investigated circulating SARS-CoV-2−specific CD8 + T cells from COVID-19 patients. For two HLA-A*02:01 SARS-CoV-2−specific CD8 + T cell epitopes, we found that, while ex vivo frequencies of responding T cells were approximately fivefold higher than for pre−COVID-19 samples, they were ∼10-fold lower than for influenza or EBV-specific memory CD8 + T cells. Additionally, SARS-CoV-2−specific CD8 + T cells recovered from convalescent COVID-19 patients had an atypically high prevalence of stem cell memory, central memory, and naïve phenotypes. Might this unexpectedly low prevalence of classical effector memory T cells be a negative consequence of the infectious process that could be avoided by prior priming with an appropriately constituted vaccine?