Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals

Cell. 2020 Jun 25;181(7):1489-1501.e15. doi: 10.1016/j.cell.2020.05.015. Epub 2020 May 20.

Abstract

Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide "megapools," circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating "common cold" coronaviruses and SARS-CoV-2.

Keywords: CD4; CD8; COVID-19; SARS-CoV-2; T cells; coronavirus; cross-reactivity; epitopes.

MeSH terms

  • Betacoronavirus / genetics
  • Betacoronavirus / physiology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Convalescence
  • Coronavirus Infections / blood
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / virology
  • Cross Reactions
  • Epitopes, T-Lymphocyte*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Proteins / metabolism
  • Viral Vaccines / immunology

Substances

  • COVID-19 vaccine
  • Epitopes, T-Lymphocyte
  • Spike Glycoprotein, Coronavirus
  • Viral Proteins
  • Viral Vaccines
  • spike protein, SARS-CoV-2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2