Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

Science. 2020 Oct 2;370(6512):89-94. doi: 10.1126/science.abd3871. Epub 2020 Aug 4.

Abstract

Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2-reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in coronavirus disease 2019 (COVID-19) disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus / genetics
  • Betacoronavirus / immunology*
  • Blood Donors
  • CD4-Positive T-Lymphocytes / immunology*
  • COVID-19
  • Coronavirus Infections / immunology*
  • Cross Reactions
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Genome, Viral
  • Humans
  • Immunologic Memory*
  • Open Reading Frames
  • Pandemics
  • Pneumonia, Viral / immunology*
  • SARS-CoV-2
  • Sequence Homology

Substances

  • Epitopes, T-Lymphocyte