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

tetano

Editor, Senior Moderator
Cell Rep


. 2021 Dec 17;110214.
doi: 10.1016/j.celrep.2021.110214. Online ahead of print.
Recruitment of highly cytotoxic CD8 [SUP]+[/SUP] T cell receptors in mild SARS-CoV-2 infection


Karolin I Wagner[SUP] 1 [/SUP], Laura M Mateyka[SUP] 1 [/SUP], Sebastian Jarosch[SUP] 1 [/SUP], Vincent Grass[SUP] 2 [/SUP], Simone Weber[SUP] 1 [/SUP], Kilian Schober[SUP] 3 [/SUP], Monika Hammel[SUP] 1 [/SUP], Teresa Burrell[SUP] 1 [/SUP], Behnam Kalali[SUP] 1 [/SUP], Holger Poppert[SUP] 4 [/SUP], Henriette Beyer[SUP] 5 [/SUP], Sophia Schambeck[SUP] 6 [/SUP], Stefan Holdenrieder[SUP] 7 [/SUP], Andrea Strötges-Achatz[SUP] 7 [/SUP], Verena Haselmann[SUP] 8 [/SUP], Michael Neumaier[SUP] 8 [/SUP], Johanna Erber[SUP] 9 [/SUP], Alina Priller[SUP] 10 [/SUP], Sarah Yazici[SUP] 10 [/SUP], Hedwig Roggendorf[SUP] 10 [/SUP], Marcus Odendahl[SUP] 11 [/SUP], Torsten Tonn[SUP] 11 [/SUP], Andrea Dick[SUP] 12 [/SUP], Klaus Witter[SUP] 12 [/SUP], Hrvoje Mijočević[SUP] 2 [/SUP], Ulrike Protzer[SUP] 13 [/SUP], Percy A Knolle[SUP] 14 [/SUP], Andreas Pichlmair[SUP] 13 [/SUP], Claudia S Crowell[SUP] 15 [/SUP], Markus Gerhard[SUP] 15 [/SUP], Elvira D'Ippolito[SUP] 16 [/SUP], Dirk H Busch[SUP] 17 [/SUP]



Affiliations

Abstract

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[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cell immunity.

Keywords: CD8(+) T cells; SARS-CoV-2 infection; T cell immunity; T cell receptor; TCR engineering; TCR identification; cytotoxic T cells; mild COVID-19; scRNA sequencing.
 
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