Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells

Nat Med. 2021 Jan;27(1):78-85. doi: 10.1038/s41591-020-01143-2. Epub 2020 Nov 12.


Emerging data indicate that SARS-CoV-2-specific CD8+ T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals1-5. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8+ T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8+ T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8+ T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8+ T cells exhibited functional characteristics comparable to influenza-specific CD8+ T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8+ T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / blood
  • COVID-19 / immunology*
  • Case-Control Studies
  • Convalescence
  • Coronavirus Nucleocapsid Proteins / chemistry
  • Cross Reactions
  • Cross-Sectional Studies
  • Epitopes, T-Lymphocyte
  • Flow Cytometry
  • HLA-B Antigens / immunology
  • Humans
  • Immunologic Memory
  • Longitudinal Studies
  • Phosphoproteins / chemistry
  • SARS-CoV-2 / physiology
  • Spike Glycoprotein, Coronavirus / chemistry


  • Coronavirus Nucleocapsid Proteins
  • Epitopes, T-Lymphocyte
  • HLA-B Antigens
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2