Projects per year
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.
Original language | English |
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Article number | 2931 |
Number of pages | 20 |
Journal | Nature Communications |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 18 May 2021 |
Projects
- 5 Finished
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Understanding the complexity of antigen presentation
Purcell, A. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/18 → 31/12/22
Project: Research
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The role of cross-reactive T cells in severe lung disease following viral respiratory infections
Purcell, A. (Primary Chief Investigator (PCI)), Kotsimbos, T. (Chief Investigator (CI)) & Mifsud, N. (Chief Investigator (CI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/15 → 31/12/18
Project: Research
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Limiting the impact of influenza
Turner, S. (Primary Chief Investigator (PCI)), La Gruta, N. (Chief Investigator (CI)), Chen, W. (Chief Investigator (CI)), Kedzierska, K. (Chief Investigator (CI)), Jackson, D. (Chief Investigator (CI)), Brown, L. E. (Chief Investigator (CI)) & Doherty, P. C. (Chief Investigator (CI))
1/01/15 → 31/12/19
Project: Research
Equipment
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Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility