Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

Nat Immunol. 2020 Nov;21(11):1336-1345. doi: 10.1038/s41590-020-0782-6. Epub 2020 Sep 4.

Abstract

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

Publication types

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

MeSH terms

  • Antigens, Viral / immunology*
  • Betacoronavirus / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology
  • Coronavirus Infections / prevention & control
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunologic Memory / immunology*
  • Pandemics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology
  • Spike Glycoprotein, Coronavirus / immunology
  • United Kingdom
  • Viral Vaccines / immunology

Substances

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

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2