Functional consequences of HLA-DQ8 homozygosity versus heterozygosity for islet autoimmunity in type 1 diabetes

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dc.contributor.authorEerligh, P.en
dc.contributor.authorvan Lummel, M.en
dc.contributor.authorZaldumbide, A.en
dc.contributor.authorMoustakas, A. K.en
dc.contributor.authorDuinkerken, G.en
dc.contributor.authorBondinas, G.en
dc.contributor.authorKoeleman, B. P.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorRoep, B. O.en
dc.date.accessioned2015-11-24T19:15:13Z
dc.date.available2015-11-24T19:15:13Z
dc.identifier.issn1476-5470-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/21478
dc.rightsDefault Licence-
dc.subjectAdolescenten
dc.subjectB-Lymphocytes/cytology/immunologyen
dc.subjectDiabetes Mellitus, Type 1/genetics/immunology/*metabolismen
dc.subjectEpitopes, B-Lymphocyte/immunologyen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectHLA-DQ Antigens/*geneticsen
dc.subjectHeterozygoteen
dc.subjectHomozygoteen
dc.subjectHumansen
dc.subjectInsulin/geneticsen
dc.subjectIslets of Langerhans/*immunologyen
dc.subjectMaleen
dc.subjectProtein Bindingen
dc.subjectSyndecans/metabolismen
dc.subjectT-Lymphocytes/cytology/immunologyen
dc.subjectThymosin/metabolismen
dc.titleFunctional consequences of HLA-DQ8 homozygosity versus heterozygosity for islet autoimmunity in type 1 diabetesen
heal.abstractHuman leukocyte antigen (HLA) class II haplotypes are established risk factors in type 1 diabetes (T1D). The heterozygous DQ2/8 genotype confers the highest risk, whereas the DQ6/8 genotype is protective. We hypothesized that DQ2/8 trans-molecules composed of alpha and beta chains from DQ2 and DQ8 express unique beta-cell epitopes, whereas DQ6 may interfere with peptide binding to DQ8. Here we show that a single insulin epitope (InsB13-21) within the T1D prototype antigenic InsB6-22 peptide can bind to both cis- and trans-dimers, although these molecules display different peptide binding patterns. DQ6 binds a distinct insulin epitope (InsB6-14). The phenotype of DQ8-restricted T cells from a T1D patient changed from proinflammatory to anti-inflammatory in the presence of DQ6. Our data provide new insights into both susceptible and protective mechanism of DQ, where protecting HLA molecules bind autoantigens in a different (competing) binding register leading to 'epitope stealing', thereby inducing a regulatory, rather than a pathogenic immune response.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1038/gene.2011.24-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/21562577-
heal.journalNameGenes Immunen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2011-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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