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

T cell immunity is crucial for the control of SARS-CoV-2 infections and has been widely studied on a quantitative level. However, quality of responses, in particular of CD8+ T cells, has only been marginally investigated so far. Here, we isolated T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common Human Leucocyte Antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells were detected up to twelve months from infection. TCR repertoires were diverse, with heterogeneous functional avidity and cytotoxicity towards virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlated 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 – classical features of protective immunity - are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality and to potentially restore functional CD8+ T cell immunity. scRNA sequencing data for single SARS-CoV-2 peptide-stimulated CD8 T cell samples from convalescent donors