An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease

Nat Immunol. 2022 Jan;23(1):50-61. doi: 10.1038/s41590-021-01084-z. Epub 2021 Dec 1.

Abstract

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Publication types

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

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Antibodies, Viral / immunology
  • Antibody Affinity / immunology
  • COVID-19 / immunology
  • COVID-19 / pathology
  • Cell Line, Transformed
  • Female
  • Gene Expression Profiling
  • HLA-B7 Antigen / immunology*
  • Humans
  • Immunodominant Epitopes / immunology*
  • Immunologic Memory / immunology
  • Male
  • Middle Aged
  • Nucleocapsid Proteins / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • SARS-CoV-2 / immunology*
  • Severity of Illness Index
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Vaccinia virus / metabolism

Substances

  • Antibodies, Viral
  • HLA-B*07:02 antigen
  • HLA-B7 Antigen
  • Immunodominant Epitopes
  • Nucleocapsid Proteins
  • Receptors, Antigen, T-Cell

Supplementary concepts

  • SARS-CoV-2 variants