Peptide analysis, stability studies, and structural modeling explain contradictory peptide motifs and unique properties of the NOD mouse MHC class II molecule H2-A(g7)

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dc.contributor.authorMunz, C.en
dc.contributor.authorHofmann, M.en
dc.contributor.authorYoshida, K.en
dc.contributor.authorMoustakas, A. K.en
dc.contributor.authorKikutani, H.en
dc.contributor.authorStevanovic, S.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorRammensee, H. G.en
dc.date.accessioned2015-11-24T18:59:46Z
dc.date.available2015-11-24T18:59:46Z
dc.identifier.issn0014-2980-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19406
dc.rightsDefault Licence-
dc.subjectAmino Acid Motifsen
dc.subjectAmino Acid Sequenceen
dc.subjectAnimalsen
dc.subjectCell Lineen
dc.subjectDiabetes Mellitus, Type 1/genetics/*immunologyen
dc.subjectHistocompatibility Antigens Class II/analysis/*chemistryen
dc.subjectMiceen
dc.subjectMice, Inbred NODen
dc.subjectModels, Structuralen
dc.subjectMolecular Sequence Dataen
dc.titlePeptide analysis, stability studies, and structural modeling explain contradictory peptide motifs and unique properties of the NOD mouse MHC class II molecule H2-A(g7)en
heal.abstractThe MHC class II molecule H2-A(g7) is the chief genetic determinant in insulin-dependent diabetes mellitus of the non-obese diabetic (NOD) mice. Poor peptide binding ability, as well as presentation of a unique subset of peptides by this molecule was suggested to promote autoimmunity in this strain. However, several laboratories have presented results in favor of an H2-A(g7) molecule that can avidly bind many different peptides. The crystal structures of H2-A(g7) in complex with two different peptides did not completely resolve this issue. To analyze the peptide binding capacity and the motif requirements of H2-A(g7), we eluted natural ligands from purified H2-A(g7) molecules isolated from the H2-A(g7)-transfected M12-C3 cells. A low peptide yield dominated by a few peptide ligands was found. Pool sequencing and alignment of individual ligands on the basis of molecular modeling revealed a peptide-binding motif with basic/aliphatic/small hydrophilic amino acids at relative position 1 (p1), aliphatic amino acids at p4, Ala at p6, and acidic amino acids and Ser/Gly at p9, as well as acidic residues at p10/11. Though weak, the binding of individual ligands, as well as the importance of an acidic C-terminal residue was confirmed by peptide binding studies to isolated H2-A(g7) molecules. Furthermore, the H2-A(g7) molecule incompletely dissociated into its constituent chains in SDS-electrophoresis under nonreducing conditions. This provides additional evidence of its weak affinity for peptides, which probably arises from the combination of beta56His/beta57Ser/beta78Ala and other unique H2-A(g7) residues in contact with the antigenic peptide. These results allow a better understanding of the role of this molecule in the development of autoimmunity and the identification of epitopes relevant to diabetes.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1002/1521-4141(200208)32:8<2105::AID-IMMU2105>3.0.CO;2-Q-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/12209622-
heal.identifier.secondaryhttp://onlinelibrary.wiley.com/store/10.1002/1521-4141(200208)32:8<2105::AID-IMMU2105>3.0.CO;2-Q/asset/2105_ftp.pdf?v=1&t=h0ustzd0&s=7a6c29c79d6fe9373d459190278fbbf9a64d24ff-
heal.journalNameEur J Immunolen
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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