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

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journal contribution
posted on 2024-11-21, 01:04 authored by L Hensen, PT Illing, E Bridie Clemens, THO Nguyen, M Koutsakos, CE van de Sandt, NA Mifsud, AT Nguyen, C Szeto, BY Chua, H Halim, S Rizzetto, F Luciani, L Loh, EJ Grant, PM Saunders, AG Brooks, S Rockman, TC Kotsimbos, AC Cheng, M Richards, GP Westall, LM Wakim, T Loudovaris, SI Mannering, M Elliott, SG Tangye, DC Jackson, Katie FlanaganKatie Flanagan, J Rossjohn, S Gras, J Davies, A Miller, SYC Tong, AW Purcell, K Kedzierska
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.

History

Publication title

Nature Communications

Volume

12

Issue

1

Article number

2931

Number

2931

Pagination

1-20

ISSN

2041-1723

Department/School

Medicine

Publisher

Nature Pub. Group

Publication status

  • Published

Place of publication

United Kingdom

Rights statement

Copyright 2021 The Authors. Licensed under Creative Common Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Socio-economic Objectives

200105 Treatment of human diseases and conditions, 210302 Aboriginal and Torres Strait Islander health status and outcomes

UN Sustainable Development Goals

3 Good Health and Well Being

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