What question did this study set out to answer?

This research aims to explore the differences in CD8+ T-cell responses against influenza in Indigenous and non-Indigenous people with HLA-A*24:02.

May 18, 2021Open Access

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

Key Points

This research aims to explore the differences in CD8+ T-cell responses against influenza in Indigenous and non-Indigenous people with HLA-A*24:02.
Characterization of CD8+ T cell responses using human tissues and samples from patients infected with influenza A and B.
Identification of immunodominant CD8+ T-cell epitopes relevant to HLA-A*24:02.
Comparison of T cell landscapes in Indigenous Australians and non-Indigenous individuals.
Identified one immunodominant epitope for influenza A and six for influenza B, with significant CD8+ T-cell cross-reactivity.
Detected memory CD8+ T cells with specific phenotypes in healthy individuals, and effector T cells in influenza patients.
Findings support the development of T-cell-mediated vaccines targeting diverse CD8+ T-cell responses.

Abstract

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/PB2 550–558 -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.

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