Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection.

T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8⁺ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8⁺ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8⁺ TCRs—classic features of protective immunity—are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8⁺ T cell immunity. [Display omitted] • SARS-CoV-2-specific CD8⁺ T cells are detectable up to 12 months after infection • scRNA sequencing reveals polyclonal CD8⁺ T cells with variable functionalities • High-avidity CD8⁺ T cells engineered with SARS-CoV-2-specific TCRs are cytotoxic • Single cell signature for highly functional SARS-CoV-2-specific CD8⁺ T cells Wagner et al. detect CD8⁺ T cell responses to diverse immunodominant SARS-CoV-2-specific epitopes. scRNA sequencing of epitope-responsive CD8⁺ T cells reveals a polyclonal T cell receptor repertoire. State-of-the-art TCR re-expression confirms a highly specific and functional T cell response in convalescent mild COVID-19. [ABSTRACT FROM AUTHOR]