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dc.contributor.authorMatthews, Philippa C.
dc.contributor.authorListgarten, Jennifer
dc.contributor.authorCarlson, Jonathan M.
dc.contributor.authorPayne, Rebecca
dc.contributor.authorHuang, Kuan-Hsiang Gary
dc.contributor.authorFrater, John
dc.contributor.authorGoedhals, Dominique
dc.contributor.authorSteyn, Dewald
dc.contributor.authorvan Vuuren, Cloete
dc.contributor.authorPaioni, Paolo
dc.contributor.authorJooste, Pieter
dc.contributor.authorOgwu, Anthony
dc.contributor.authorShapiro, Roger L.
dc.contributor.authorMncube, Zenele
dc.contributor.authorNdung'u, Thumbi
dc.contributor.authorWalker, Bruce David
dc.contributor.authorHeckerman, David
dc.contributor.authorGoulder, Philip J. R.
dc.date.accessioned2013-04-08T18:42:09Z
dc.date.issued2012
dc.identifier.citationMatthews, Philippa C., Jennifer Listgarten, Jonathan M. Carlson, Rebecca Payne, Kuan-Hsiang Gary Huang, John Frater, Dominique Goedhals, et al. 2012. Co-operative additive effects between HLA alleles in control of HIV-1. PLoS ONE 7(10): e47799.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10511100
dc.description.abstractBackground: HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles - irrespective of linkage disequilibrium - function co-operatively. Methodology/Principal Findings: We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate ‘co-operative additive’ effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q<0.05 in each case). We developed a novel ‘sharing score’ to quantify the breadth of CD8+ T cell responses made by pairs of HLA alleles across the HIV proteome, and used this to demonstrate that successful viraemic suppression correlates with breadth of unique CD8+ T cell responses (p = 0.03). Conclusions/Significance: These results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0047799en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477121/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectImmunologyen_US
dc.subjectImmune Cellsen_US
dc.subjectT Cellsen_US
dc.subjectMedicineen_US
dc.subjectClinical Immunologyen_US
dc.subjectImmunityen_US
dc.subjectAdaptive Immunityen_US
dc.subjectImmune Defenseen_US
dc.subjectImmune Responseen_US
dc.subjectMajor Histocompatibility Complexen_US
dc.subjectInfectious Diseasesen_US
dc.subjectViral Diseasesen_US
dc.subjectHIVen_US
dc.subjectRetrovirology and HIV immunopathogenesisen_US
dc.subjectObstetrics and Gynecologyen_US
dc.subjectGenitourinary Infectionsen_US
dc.subjectUrologyen_US
dc.titleCo-Operative Additive Effects between HLA Alleles in Control of HIV-1en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorShapiro, Roger L.
dc.date.available2013-04-08T18:42:09Z
dc.identifier.doi10.1371/journal.pone.0047799*
dash.authorsorderedfalse
dash.contributor.affiliatedOgwu, Anthony
dash.contributor.affiliatedShapiro, Roger
dash.contributor.affiliatedWalker, Bruce
dc.identifier.orcid0000-0001-6122-9245


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