Journal article
HLA targeting efficiency correlates with human T-cell response magnitude and with mortality from influenza A infection
Proceedings of the National Academy of Sciences, Vol.110(33), pp.13492-13497
2013
Abstract
Experimental and computational evidence suggests that HLAs preferentially bind conserved regions of viral proteins, a concept we term “targeting efficiency,” and that this preference may provide improved clearance of infection in several viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were measured from peripheral blood mononuclear cells obtained from a household cohort study performed during the 2009–2010 influenza season. We found that HLA targeting efficiency scores significantly correlated with IFN-γ enzyme-linked immunosorbent spot responses (P = 0.042, multiple regression). A further population-based analysis found that the carriage frequencies of the alleles with the lowest targeting efficiencies, A*24, were associated with pH1N1 mortality (r = 0.37, P = 0.031) and are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use are associated with CD8 T-cell magnitude in humans after influenza infection. The computational tools used in this study may be useful predictors of potential morbidity and identify immunologic differences of new variant influenza strains more accurately than evolutionary sequence comparisons. Population-based studies of the relative frequency of these alleles in severe vs. mild influenza cases might advance clinical practices for severe H1N1 infections among genetically susceptible populations.
Details
- Title
- HLA targeting efficiency correlates with human T-cell response magnitude and with mortality from influenza A infection
- Authors/Creators
- T. Hertz (Author/Creator) - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaC.M. Oshansky (Author/Creator) - St. Jude Children's Research HospitalP.L. Roddam (Author/Creator) - University of Tennessee Health Science CenterJ.P. DeVincenzo (Author/Creator) - University of Tennessee Health Science CenterM.A. Caniza (Author/Creator) - St. Jude Children's Research HospitalN. Jojic (Author/Creator) - Microsoft (United States)S. Mallal (Author/Creator) - Royal Perth HospitalE. Phillips (Author/Creator) - Royal Perth HospitalI. James (Author/Creator) - Royal Perth HospitalM.E. Halloran (Author/Creator) - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaP.G. Thomas (Author/Creator) - St. Jude Children's Research HospitalL. Corey (Author/Creator) - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
- Publication Details
- Proceedings of the National Academy of Sciences, Vol.110(33), pp.13492-13497
- Publisher
- National Academy of Sciences
- Identifiers
- 991005541897707891
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.104 Virology - General
- 1.104.126 Influenza
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology