Type 1 Diabetes-associated HLA-DQ8 Transdimer Accommodates a Unique Peptide Repertoire

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dc.contributor.authorvan Lummel, M.en
dc.contributor.authorvan Veelen, P. A.en
dc.contributor.authorZaldumbide, A.en
dc.contributor.authorde Ru, A.en
dc.contributor.authorJanssen, G. M.en
dc.contributor.authorMoustakas, A. K.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorDrijfhout, J. W.en
dc.contributor.authorRoep, B. O.en
dc.contributor.authorKoning, F.en
dc.date.accessioned2015-11-24T19:01:16Z
dc.date.available2015-11-24T19:01:16Z
dc.identifier.issn1083-351X-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19665
dc.rightsDefault Licence-
dc.titleType 1 Diabetes-associated HLA-DQ8 Transdimer Accommodates a Unique Peptide Repertoireen
heal.abstractHLA-DQ2 and HLA-DQ8 are strongly predisposing haplotypes for type 1 diabetes (T1D). Yet HLA-DQ2/8 heterozygous individuals have a synergistically increased risk compared with HLA-DQ2 or HLA-DQ8 homozygote subjects that may result from the presence of a transdimer formed between the alpha-chain of HLA-DQ2 (DQA1*05:01) and the beta-chain of HLA-DQ8 (DQB1*03:02). We generated cells exclusively expressing this transdimer (HLA-DQ8trans), characterized its peptide binding repertoire, and defined a unique transdimer-specific peptide binding motif that was found to be distinct from those of HLA-DQ2 and HLA-DQ8. This motif predicts an array of peptides of islet autoantigens as candidate T cell epitopes, many of which selectively bind to the HLA transdimer, whereas others bind to both HLA-DQ8 and transdimer with similar affinity. Our findings provide a molecular basis for the association between HLA-DQ transdimers and T1D and set the stage for rational testing of potential diabetogenic peptide epitopes.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1074/jbc.M111.313940-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/22184118-
heal.identifier.secondaryhttp://www.jbc.org/content/287/12/9514-
heal.journalNameJ Biol Chemen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2012-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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