PMID- 26493179 OWN - NLM STAT- MEDLINE DCOM- 20161223 LR - 20211203 IS - 1440-1711 (Electronic) IS - 0818-9641 (Print) IS - 0818-9641 (Linking) VI - 94 IP - 4 DP - 2016 Apr TI - Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians. PG - 367-77 LID - 10.1038/icb.2015.93 [doi] AB - Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying mechanisms are unknown. We studied immune and genetic factors that could predicate severe influenza disease in Indigenous Australians enrolled in the LIFT study: looking into influenza T-cell immunity. To examine CD8(+) T-cell immunity, we characterised human leukocyte antigen (HLA) profiles. HLA typing confirmed previous studies showing predominant usage of HLA-A*02:01, 11:01, 24:02, 34:01 and HLA-B*13:01, 15:21, 40:01/02, 56:01/02 in Indigenous Australians. We identified two new HLA alleles (HLA-A*02:new and HLA-B*56:new). Modelling suggests that variations within HLA-A*02:new (but not HLA-B56:new) could affect peptide binding. There is a relative lack of known influenza epitopes for the majority of these HLAs, with the exception of a universal HLA-A*02:01-M158 epitope and proposed epitopes presented by HLA-A*11:01/HLA-A*24:02. To dissect universal CD8(+) T-cell responses, we analysed the magnitude, function and T-cell receptor (TCR) clonality of HLA-A*02:01-M158(+)CD8(+) T cells. We found comparable IFN-gamma, TNF and CD107a and TCRalphabeta characteristics in Indigenous and non-Indigenous Australians, suggesting that the ~15% of Indigenous people that express HLA-A*02:01 have universal influenza-specific CD8(+) T-cell immunity. Furthermore, the frequency of an influenza host risk factor, IFITM3-C/C, was comparable between Indigenous Australians and Europeans, suggesting that expression of this allele does not explain increased disease severity at a population level. Our study indicates a need to identify novel influenza-specific CD8(+) T-cell epitopes restricted by HLA-A and HLA-B alleles prevalent in Indigenous populations for the rational design of universal T-cell vaccines. FAU - Clemens, E Bridie AU - Clemens EB AD - Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. FAU - Grant, Emma J AU - Grant EJ AD - Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. FAU - Wang, Zhongfang AU - Wang Z AD - Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. FAU - Gras, Stephanie AU - Gras S AD - Infection and Immunity Program, Biomedicine Discovery Institute and The Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia. AD - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia. FAU - Tipping, Peta AU - Tipping P AD - Menzies School of Health Research, Darwin, Northern Territory, Australia. FAU - Rossjohn, Jamie AU - Rossjohn J AD - Infection and Immunity Program, Biomedicine Discovery Institute and The Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia. AD - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia. AD - Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. FAU - Miller, Adrian AU - Miller A AD - Indigenous Research Network, Griffith University, Brisbane, Queensland, Australia. FAU - Tong, Steven Y C AU - Tong SY AD - Menzies School of Health Research, Darwin, Northern Territory, Australia. FAU - Kedzierska, Katherine AU - Kedzierska K AD - Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151023 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (IFITM3 protein, human) RN - 0 (Influenza Vaccines) RN - 0 (Lysosomal-Associated Membrane Protein 1) RN - 0 (M1 protein, Influenza A virus) RN - 0 (Membrane Proteins) RN - 0 (RNA-Binding Proteins) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Viral Matrix Proteins) RN - 82115-62-6 (Interferon-gamma) SB - IM EIN - Immunol Cell Biol. 2017 Aug;95(7):648. PMID: 28785057 MH - Adult MH - Alleles MH - CD8-Positive T-Lymphocytes/*physiology MH - Cells, Cultured MH - Epitopes, T-Lymphocyte/metabolism MH - Female MH - HLA Antigens/*genetics MH - Histocompatibility Testing MH - Humans MH - Influenza Vaccines MH - Influenza, Human/genetics/*immunology MH - Interferon-gamma/metabolism MH - Lysosomal-Associated Membrane Protein 1/metabolism MH - Male MH - Membrane Proteins/metabolism MH - Middle Aged MH - *Native Hawaiian or Other Pacific Islander MH - RNA-Binding Proteins/metabolism MH - Receptors, Antigen, T-Cell, alpha-beta/genetics MH - Risk MH - Tumor Necrosis Factor-alpha/metabolism MH - Viral Matrix Proteins/metabolism PMC - PMC4840236 EDAT- 2015/10/24 06:00 MHDA- 2016/12/24 06:00 PMCR- 2016/04/22 CRDT- 2015/10/24 06:00 PHST- 2015/08/26 00:00 [received] PHST- 2015/10/14 00:00 [revised] PHST- 2015/10/15 00:00 [accepted] PHST- 2015/10/24 06:00 [entrez] PHST- 2015/10/24 06:00 [pubmed] PHST- 2016/12/24 06:00 [medline] PHST- 2016/04/22 00:00 [pmc-release] AID - icb201593 [pii] AID - 10.1038/icb.2015.93 [doi] PST - ppublish SO - Immunol Cell Biol. 2016 Apr;94(4):367-77. doi: 10.1038/icb.2015.93. Epub 2015 Oct 23.