Unbiased Screens Show CD8 + T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein

Immunity. 2020 Nov 17;53(5):1095-1107.e3. doi: 10.1016/j.immuni.2020.10.006. Epub 2020 Oct 20.


Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8+ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8+ T cell immunity to SARS-CoV-2.

Keywords: CD8+ T cells; COVID-19; SARS-CoV-2; T-Scan; immunity; immunodominant epitopes; novel coronavirus; seasonal coronaviruses; spike protein; vaccine.

MeSH terms

  • Adult
  • Aged
  • Betacoronavirus / immunology*
  • Betacoronavirus / isolation & purification
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19
  • Convalescence
  • Coronavirus / immunology
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / immunology*
  • Coronavirus Nucleocapsid Proteins
  • Epitope Mapping
  • Epitopes, T-Lymphocyte
  • Female
  • Humans
  • Immunodominant Epitopes
  • Immunologic Memory
  • Male
  • Middle Aged
  • Nucleocapsid Proteins / immunology
  • Pandemics
  • Phosphoproteins
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / immunology*
  • Polyproteins
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / immunology*
  • Viral Proteins / immunology
  • Young Adult


  • Coronavirus Nucleocapsid Proteins
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Nucleocapsid Proteins
  • ORF1ab polyprotein, SARS-CoV-2
  • Phosphoproteins
  • Polyproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Proteins
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2