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dc.contributor.authorHarrison, LC
dc.contributor.authorHoneyman, MC
dc.contributor.authorTrembleau, S
dc.contributor.authorGregori, S
dc.contributor.authorGallazzi, F
dc.contributor.authorAugstein, P
dc.contributor.authorBrusic, V
dc.contributor.authorHammer, J
dc.contributor.authorAdorini, L
dc.date.accessioned2021-02-04T01:06:14Z
dc.date.available2021-02-04T01:06:14Z
dc.date.issued1997-03-17
dc.identifier.citationHarrison, L. C., Honeyman, M. C., Trembleau, S., Gregori, S., Gallazzi, F., Augstein, P., Brusic, V., Hammer, J. & Adorini, L. (1997). A peptide-binding motif for I-A(g7), the class II major histocompatibility complex (MHC) molecule of NOD and Biozzi AB/H mice.. J Exp Med, 185 (6), pp.1013-1021. https://doi.org/10.1084/jem.185.6.1013.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/259263
dc.description.abstractThe class II major histocompatibility complex molecule I-A(g7) is strongly linked to the development of spontaneous insulin-dependent diabetes mellitus (IDDM) in non obese diabetic mice and to the induction of experimental allergic encephalomyelitis in Biozzi AB/H mice. Structurally, it resembles the HLA-DQ molecules associated with human IDDM, in having a non-Asp residue at position 57 in its beta chain. To identify the requirements for peptide binding to I-A(g7) and thereby potentially pathogenic T cell epitopes, we analyzed a known I-A(g7)-restricted T cell epitope, hen egg white lysozyme (HEL) amino acids 9-27. NH2- and COOH-terminal truncations demonstrated that the minimal epitope for activation of the T cell hybridoma 2D12.1 was M12-R21 and the minimum sequence for direct binding to purified I-A(g7) M12-Y20/K13-R21. Alanine (A) scanning revealed two primary anchors for binding at relative positions (p) 6 (L) and 9 (Y) in the HEL epitope. The critical role of both anchors was demonstrated by incorporating L and Y in poly(A) backbones at the same relative positions as in the HEL epitope. Well-tolerated, weakly tolerated, and nontolerated residues were identified by analyzing the binding of peptides containing multiple substitutions at individual positions. Optimally, p6 was a large, hydrophobic residue (L, I, V, M), whereas p9 was aromatic and hydrophobic (Y or F) or positively charged (K, R). Specific residues were not tolerated at these and some other positions. A motif for binding to I-A(g7) deduced from analysis of the model HEL epitope was present in 27/30 (90%) of peptides reported to be I-A(g7)-restricted T cell epitopes or eluted from I-A(g7). Scanning a set of overlapping peptides encompassing human proinsulin revealed the motif in 6/6 good binders (sensitivity = 100%) and 4/13 weak or non-binders (specificity = 70%). This motif should facilitate identification of autoantigenic epitopes relevant to the pathogenesis and immunotherapy of IDDM.
dc.languageeng
dc.publisherRockefeller University Press
dc.titleA peptide-binding motif for I-A(g7), the class II major histocompatibility complex (MHC) molecule of NOD and Biozzi AB/H mice.
dc.typeJournal Article
dc.identifier.doi10.1084/jem.185.6.1013
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.facultyCollected Works
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume185
melbourne.source.issue6
melbourne.source.pages1013-1021
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1209177
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196246
melbourne.contributor.authorHarrison, Leonard
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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