Modulation of T cell response to hGAD65 peptide epitopes

dc.contributor.authorMasewicz, S. A.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorSwanson, E.en
dc.contributor.authorMoriarity, L.en
dc.contributor.authorMoustakas, A. K.en
dc.contributor.authorNepom, G. T.en
dc.date.accessioned2015-11-24T19:04:08Z
dc.date.available2015-11-24T19:04:08Z
dc.identifier.issn0001-2815-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19979
dc.rightsDefault Licence-
dc.subjectEpitopes, T-Lymphocyte/chemistry/*immunologyen
dc.subjectGlutamate Decarboxylase/chemistry/*immunologyen
dc.subjectHumansen
dc.subjectIsoenzymes/chemistry/*immunologyen
dc.subjectModels, Molecularen
dc.subjectPeptides/immunology/metabolismen
dc.subjectPolymorphism, Geneticen
dc.subjectT-Lymphocytes/*immunologyen
dc.titleModulation of T cell response to hGAD65 peptide epitopesen
heal.abstractHuman CD4 T cell responses to an epitope of hGAD65 (GAD = glutamic acid decarboxylase), residues 555-567, are modulated by interaction with an altered peptide ligand containing modifications at TCR contact residues. Using different HLA-DR4 molecules with polymorphisms at sites corresponding to peptide binding pockets p1 and p9, we tested the effect of additional modifications in the altered peptide ligand (APL) designed to increase the avidity of the MHC-peptide interaction and therefore the efficiency of TCR signaling. Modification of the peptide or the MHC molecule which enhanced the p1 interaction also enhanced the antagonist activity of the modified APL. In contrast, modifications at p9 led to a reversal in APL function, resulting in agonist activity. Molecular homology modeling of these MHC-peptide interactions suggests a structural basis for this functional dichotomy in which topographically remote variations lead to unique interaction effects.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/12028536-
heal.identifier.secondaryhttp://onlinelibrary.wiley.com/store/10.1034/j.1399-0039.2002.590205.x/asset/j.1399-0039.2002.590205.x.pdf?v=1&t=h0usmxvx&s=53598752851feb13f424e75ea33f3f8beff01ad3-
heal.journalNameTissue Antigensen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2002-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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