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

2021; Cell Press; Volume: 38; Issue: 2 Linguagem: Inglês

10.1016/j.celrep.2021.110214

2639-1856

K Wagner, Laura M. Mateyka, Sebastian Jarosch, Vincent Grass, Simone Weber, Kilian Schober, Monika Hammel, Teresa Burrell, Behnam Kalali, Holger Poppert, Henriette Beyer, Sophia E. Schambeck, Stefan Holdenrieder, Andrea Strötges-Achatz, Verena Haselmann, Michael Neumaier, Johanna Erber, Alina Priller, Sarah Yazici, Hedwig Roggendorf, Marcus Odendahl, Torsten Tonn, Andrea Dick, K. Witter, Hrvoje Mijočević, Ulrike Protzer, Percy A. Knolle, Andreas Pichlmair, Claudia S. Crowell, Markus Gerhard, Elvira D’Ippolito, Dirk H. Busch,

Long-Term Effects of COVID-19

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.