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

E Bridie Clemens, Emma J Grant, Zhongfang Wang, Stephanie Gras, Peta Tipping, Jamie Rossjohn, Adrian Miller, Steven Y C Tong, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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-?, TNF and CD107a and TCRa? 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.
Original languageEnglish
Pages (from-to)367-377
Number of pages11
JournalImmunology and Cell Biology
Volume94
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016

Cite this

Clemens, E Bridie ; Grant, Emma J ; Wang, Zhongfang ; Gras, Stephanie ; Tipping, Peta ; Rossjohn, Jamie ; Miller, Adrian ; Tong, Steven Y C ; Kedzierska, Katherine. / Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians. In: Immunology and Cell Biology. 2016 ; Vol. 94, No. 4. pp. 367-377.
@article{0a6bf06bfa6b47739b772516947ae261,
title = "Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians",
abstract = "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-?, TNF and CD107a and TCRa? 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.",
author = "Clemens, {E Bridie} and Grant, {Emma J} and Zhongfang Wang and Stephanie Gras and Peta Tipping and Jamie Rossjohn and Adrian Miller and Tong, {Steven Y C} and Katherine Kedzierska",
year = "2016",
month = "4",
day = "1",
doi = "10.1038/icb.2015.93",
language = "English",
volume = "94",
pages = "367--377",
journal = "Immunology and Cell Biology",
issn = "0818-9641",
publisher = "Nature Publishing Group",
number = "4",

}

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; Kedzierska, Katherine.

In: Immunology and Cell Biology, Vol. 94, No. 4, 01.04.2016, p. 367-377.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians

AU - Clemens, E Bridie

AU - Grant, Emma J

AU - Wang, Zhongfang

AU - Gras, Stephanie

AU - Tipping, Peta

AU - Rossjohn, Jamie

AU - Miller, Adrian

AU - Tong, Steven Y C

AU - Kedzierska, Katherine

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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-?, TNF and CD107a and TCRa? 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.

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-?, TNF and CD107a and TCRa? 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.

UR - http://www.nature.com/icb/journal/vaop/ncurrent/pdf/icb201593a.pdf

U2 - 10.1038/icb.2015.93

DO - 10.1038/icb.2015.93

M3 - Article

VL - 94

SP - 367

EP - 377

JO - Immunology and Cell Biology

JF - Immunology and Cell Biology

SN - 0818-9641

IS - 4

ER -