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

journal contribution
posted on 02.11.2020, 00:00 by EB Clemens, EJ Grant, Z Wang, S Gras, P Tipping, J Rossjohn, Adrian MillerAdrian Miller, SYC Tong, K Kedzierska
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. © 2016 Australasian Society for Immunology Inc.

Funding

Category 1 - Australian Competitive Grants (this includes ARC, NHMRC)

History

Volume

94

Issue

4

Start Page

367

End Page

377

Number of Pages

11

eISSN

1440-1711

ISSN

0818-9641

Publisher

John Wiley & Sons

Additional Rights

CC BY-NC-SA 3.0

Peer Reviewed

Yes

Open Access

Yes

Cultural Warning

This research output may contain the names and images of Aboriginal and Torres Strait Islander people now deceased. We apologize for any distress that may occur.

Acceptance Date

15/10/2015

External Author Affiliations

University of Melbourne; Monash University; Menzies School of Health Research, NT

Era Eligible

Yes

Journal

Immunology and Cell Biology