SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors

Immunity. 2020 Dec 15;53(6):1245-1257.e5. doi: 10.1016/j.immuni.2020.11.004. Epub 2020 Nov 13.


Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion or activation of preexisting immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4+ and CD8+ T cell responses to the spike protein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.

Keywords: COVID-19; HLA-A∗02:01; MHC; SARS-CoV-2; Spike; T cell epitopes; T cell receptor; T cell response; TCR sequencing; clonal structure.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / metabolism
  • Asymptomatic Infections
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • Cells, Cultured
  • Convalescence
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Female
  • Humans
  • Immunity
  • Immunologic Memory
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Pandemics
  • Receptors, Antigen, T-Cell / metabolism
  • SARS-CoV-2 / physiology*
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Young Adult


  • Antibodies, Viral
  • Epitopes, T-Lymphocyte
  • Receptors, Antigen, T-Cell
  • Spike Glycoprotein, Coronavirus