Cell reportsDec 30, 2021

Strong-killing T cell receptors involved in mild COVID-19 infection

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Dec 28, 2025

Abstract

SARS-CoV-2-specific CD8 T cells may persist for up to 12 months after infection.

T cell receptor (TCR) repertoires specific to SARS-CoV-2 show diversity and varying effectiveness against infected cells.
High functionality of TCR correlates with specific gene signatures for each epitope-HLA combination studied.
Polyclonal, highly functional CD8 TCRs may be linked to protective immunity following mild SARS-CoV-2 infection.
The quality of T cell responses could be assessed and potentially enhanced based on these findings.

Simplified

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 CD8T 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 CD8T 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 CD8TCRs-classic features of protective immunity-are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8T cell immunity. + + + +

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Competing interests

Declaration of interests D.H.B. is co-founder of STAGE Cell Therapeutics GmbH (now Juno Therapeutics/Celgene) and T cell Factory B.V. (now Kite/Gilead). D.H.B. has a consulting contract with and receives sponsored research support from Juno Therapeutics, a Bristol Myers Squibb Company.

PubMed

Strong-killing T cell receptors involved in mild COVID-19 infection

Abstract

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Competing interests

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