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 Y.C., and Kedzierska, Katherine (2016) Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians. Immunology and Cell Biology, 94 (4). pp. 367-377.

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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 ID: 65212
Item Type: Article (Research - C1)
ISSN: 1440-1711
Copyright Information: © 2016 Australasian Society for Immunology Inc. All rights reserved. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Inter- national License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Funders: National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC AI1042662, NHMRC AI1071916, NHMRC 1023294, NHMRC 1065736, ARC FT120100416, NHMRC Aboriginal and Torres Strait Islander Health Research Scholarship
Date Deposited: 30 Nov 2020 01:29
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320406 Immunogenetics (incl. genetic immunology) @ 35%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320705 Medical virology @ 30%
45 INDIGENOUS STUDIES > 4504 Aboriginal and Torres Strait Islander health and wellbeing > 450402 Aboriginal and Torres Strait Islander biomedical and clinical sciences @ 35%
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