Identification and characterization of a SARS-CoV-2 specific CD8+ T cell response with immunodominant features

Nat Commun. 2021 May 10;12(1):2593. doi: 10.1038/s41467-021-22811-y.

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8+ T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8+ T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8+ T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8+ T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8+ T cell responses are detectable up to 5 months after recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8+ T cells during convalescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology*
  • Immunologic Memory
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Polyproteins / immunology
  • SARS-CoV-2 / immunology*
  • Viral Proteins / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Immunodominant Epitopes
  • ORF1ab polyprotein, SARS-CoV-2
  • Polyproteins
  • Viral Proteins