CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

Nat Commun. 2021 May 18;12(1):2931. doi: 10.1038/s41467-021-23212-x.

Abstract

Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550-558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these specificities are present in blood (CD27+CD45RA- phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27-CD45RA-PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Australia
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Dogs
  • Epitopes, T-Lymphocyte / genetics*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Gene Frequency
  • HLA-A24 Antigen / genetics*
  • HLA-A24 Antigen / immunology
  • Humans
  • Indigenous Peoples / genetics*
  • Influenza A virus / immunology
  • Influenza A virus / physiology
  • Influenza B virus / immunology
  • Influenza B virus / physiology
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Male
  • Mice, Transgenic
  • Middle Aged

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen