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

Autor: Emma J. Grant, Jamie Rossjohn, Stephanie Gras, Steven Y. C. Tong, Katherine Kedzierska, Peta Tipping, E. Bridie Clemens, Zhongfang Wang, Adrian Miller
Rok vydání: 2015
Předmět:
0301 basic medicine
Adult
Male
Risk
Native Hawaiian or Other Pacific Islander
Receptors
Antigen
T-Cell
alpha-beta
Immunology
Epitopes
T-Lymphocyte
Peptide binding
Disease
Human leukocyte antigen
Biology
CD8-Positive T-Lymphocytes
Severe influenza
Epitope
Indigenous
Viral Matrix Proteins
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Immune system
Antigen
HLA Antigens
Lysosomal-Associated Membrane Protein 1
Influenza
Human
Immunology and Allergy
Humans
030212 general & internal medicine
Allele
Alleles
Cells
Cultured
Genetics
Tumor Necrosis Factor-alpha
Histocompatibility Testing
Membrane Proteins
RNA-Binding Proteins
Cell Biology
Middle Aged
3. Good health
Geography
030104 developmental biology
Influenza Vaccines
Identification (biology)
Original Article
Female
Corrigendum
Zdroj: Immunology and Cell Biology
ISSN: 1440-1711
0818-9641
Popis: 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.
Databáze: OpenAIRE
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