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Wagner, Karolin I.; Mateyka, Laura M.; Jarosch, Sebastian; Grass, Vincent; Weber, Simone; Schober, Kilian; Hammel, Monika; Burrell, Teresa; Kalali, Behnam; Poppert, Holger; Beyer, Henriette; Schambeck, Sophia; Holdenrieder, Stefan; Strotges-Achatz, Andrea; Haselmann, Verena; Neumaier, Michael; Erber, Johanna; Priller, Alina; Yazici, Sarah; Roggendorf, Hedwig; Odendahl, Marcus; Tonn, Torsten; Dick, Andrea; Witter, Klaus; Mijocevic, Hrvoje; Protzer, Ulrike; Knolle, Percy A.; Pichlmair, Andreas; Crowell, Claudia S.; Gerhard, Markus; D'Ippolito, Elvira and Busch, Dirk H. (2022): Recruitment of highly cytotoxic CD8(+) T cell in mild SARS-CoV-2 infection. In: Cell Reports, Vol. 38, No. 2, 110214

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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.

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