Highlights
- •SARS-CoV-2-specific CD8+ T cells are detectable up to12 months post 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
SUMMARY
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 isolate 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 are detected up to twelve months from infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity towards 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 – 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.
