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

Wagner, K. I., Mateyka, L. M., Jarosch, S., Grass, V., Weber, S., Schober, K., Hammel, M., Burrell, T., Kalali, B., Poppert, H., Beyer, H., Schambeck, S., Holdenrieder, S., Strotges-Achatz, A., Haselmann, V., Neumaier, M., Erber, J., Priller, A., Yazici, S., Roggendorf, H., Odendahl, M., Tonn, T., Dick, A., Witter, K., Mijocevic, H., Protzer, U., Knolle, P. A., Pichlmair, A., Crowell, C. S., Gerhard, M., D'Ippolito, E., and Busch, D. H. (2021). Cell Rep, 110214 [Epub ahead of print]


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.