Cell reports · 2021
Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection.
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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, Strötges-Achatz Andrea, Haselmann Verena, Neumaier Michael, Erber Johanna, Priller Alina, Yazici Sarah, Roggendorf Hedwig, Odendahl Marcus, Tonn Torsten, Dick Andrea, Witter Klaus, Mijočević Hrvoje, Protzer Ulrike, Knolle Percy A, Pichlmair Andreas, Crowell Claudia S, Gerhard Markus, D'Ippolito Elvira, Busch Dirk H
Аннотация
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.