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Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians

Clemens, E Bridie, Grant, Emma J, Wang, Zhongfang, Gras, Stephanie, Tipping, Peta, Rossjohn, Jamie, Miller, Adrian, Tong, Steven YC and Kedzierska, Katherine 2015. Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians. Immunology and Cell Biology 94 (4) , pp. 367-377. 10.1038/icb.2015.93

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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‐γ, TNF and CD107a and TCRαβ 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 0818-9641
Date of First Compliant Deposit: 10 July 2017
Date of Acceptance: 15 October 2015
Last Modified: 28 Jun 2019 04:40

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