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dc.contributor.authorClemens, E Bridie
dc.contributor.authorGrant, Emma J
dc.contributor.authorWang, Zhongfang
dc.contributor.authorGras, Stephanie
dc.contributor.authorTipping, Peta
dc.contributor.authorRossjohn, Jamie
dc.contributor.authorMiller, Adrian
dc.contributor.authorTong, Steven YC
dc.contributor.authorKedzierska, Katherine
dc.date.accessioned2018-11-01T03:09:35Z
dc.date.available2018-11-01T03:09:35Z
dc.date.issued2016
dc.identifier.issn0818-9641
dc.identifier.doi10.1038/icb.2015.93
dc.identifier.urihttp://hdl.handle.net/10072/100026
dc.description.abstractIndigenous 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom367
dc.relation.ispartofpageto377
dc.relation.ispartofissue4
dc.relation.ispartofjournalImmunology and Cell Biology
dc.relation.ispartofvolume94
dc.subject.fieldofresearchImmunology not elsewhere classified
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode110799
dc.subject.fieldofresearchcode1107
dc.subject.fieldofresearchcode0601
dc.titleTowards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.description.versionPublished
gro.rights.copyright© The Author(s) 2016. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International 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 fromthe license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
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gro.griffith.authorMiller, Adrian


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