T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1

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dc.contributor.authorStepniak, D.en
dc.contributor.authorVader, L. W.en
dc.contributor.authorKooy, Y.en
dc.contributor.authorvan Veelen, P. A.en
dc.contributor.authorMoustakas, A.en
dc.contributor.authorPapandreou, N. A.en
dc.contributor.authorEliopoulos, E.en
dc.contributor.authorDrijfhout, J. W.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorKoning, F.en
dc.date.accessioned2015-11-24T19:42:53Z
dc.date.available2015-11-24T19:42:53Z
dc.identifier.issn0093-7711-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/24702
dc.rightsDefault Licence-
dc.subjectAmino Acid Sequenceen
dc.subjectComputer Simulationen
dc.subjectDatabases, Proteinen
dc.subjectEpitopes, T-Lymphocyte/immunologyen
dc.subjectGlutens/chemistry/*immunologyen
dc.subjectHLA-DQ Antigens/genetics/*metabolismen
dc.subjectHumansen
dc.subjectLymphocyte Activationen
dc.subjectMolecular Sequence Dataen
dc.subjectPeptide Fragments/chemistry/immunology/metabolismen
dc.subjectProline/*chemistryen
dc.subjectT-Lymphocytes/*immunologyen
dc.titleT-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1en
heal.abstractRecent research has implicated a large number of gluten-derived peptides in the pathogenesis of celiac disease, a preponderantly HLA-DQ2-associated disorder. Current evidence indicates that the core of some of those peptides is ten amino acids long, while HLA class II normally accommodates nine amino acids in the binding groove. We have now investigated this in detail, using gluten-specific T-cell clones, HLA-DQ2-specific peptide-binding assays and molecular modelling. T-cell recognition of both a gamma-gliadin peptide and a low-molecular-weight glutenin peptide was found to be strictly dependent on a ten-amino acids-long peptide. Subsequent peptide-binding studies indicated that the glutenin peptide bound in a conventional p1/p9 register, with an additional proline at p-1. Testing of substitution analogues demonstrated that the nature of the amino acid at p-1 strongly influenced T-cell recognition of the peptide. Moreover, molecular modelling confirmed that the glutenin peptide binds in a p1/p9 register, and that the proline at p-1 points upward towards the T-cell receptor. Database searches indicate that a large number of potential T-cell stimulatory gluten peptides with an additional proline at relative position p-1 exist, suggesting that the recognition of other gluten peptides may depend on this proline as well. This knowledge may be of importance for the identification of additional T-cell stimulatory gluten peptides and the design of a peptide-based, tolerance-inducing therapy.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1007/s00251-005-0780-8-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/15714306-
heal.identifier.secondaryhttp://www.springerlink.com/content/1ep4daeh67dr27rr/fulltext.pdf-
heal.journalNameImmunogeneticsen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2005-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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