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Immunol Cell Biol. 2015 Oct 23. doi: 10.1038/icb.2015.93. [Epub ahead of print]
Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.
Bridie Clemens E1, Grant EJ1, Wang Z1, Gras S2,3, Tipping P4, Rossjohn J2,3,5, Miller A6, Tong SY4, Kedzierska K1.
Author information
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). Modeling 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.Immunology and Cell Biology accepted article preview online, 23 October 2015. doi:10.1038/icb.2015.93.
PMID: 26493179 [PubMed - as supplied by publisher]
Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.
Bridie Clemens E1, Grant EJ1, Wang Z1, Gras S2,3, Tipping P4, Rossjohn J2,3,5, Miller A6, Tong SY4, Kedzierska K1.
Author information
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). Modeling 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.Immunology and Cell Biology accepted article preview online, 23 October 2015. doi:10.1038/icb.2015.93.
PMID: 26493179 [PubMed - as supplied by publisher]