SARS-CoV-2-reactive T-cell receptors isolated from convalescent COVID-19 patients confer potent T-cell effector function

Eur J Immunol. 2021 Nov;51(11):2651-2664. doi: 10.1002/eji.202149290. Epub 2021 Sep 13.


Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells-with the indispensable help of CD4+ T cells-are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8+ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; T-cell receptor; single-cell sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Humans
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • SARS-CoV-2 / immunology*
  • T-Lymphocytes / immunology*


  • Epitopes, T-Lymphocyte
  • Receptors, Antigen, T-Cell