title: Myelin basic protein peptide complexes with the class II MHC molecules I-Au and I-Ak form and dissociate rapidly at neutral pH.
abstract: The acetylated N-terminal peptide of myelin basic protein (MBP) is the immunodominant T cell epitope in the induction of experimental autoimmune encephalomyelitis in the I-Au- and I-Ak-expressing mouse strains. We used a direct binding assay to examine the kinetics of binding and dissociation of a series of MBP peptide analogues with the affinity-purified class II MHC molecules I-Au and I-Ak. We observe much faster in vitro rates of binding and dissociation than has been reported previously for other immunogenic peptides at neutral pH. The kinetics also reveal inactivation of the peptide-free class II MHC molecules. These results are consistent with previously proposed mechanisms for tolerance escape and autoimmune disease.
authors.affiliation: Department of Chemistry, Stanford University, CA 94305, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mason
authors.forename: D W
authors.initials: DW
authors.lastname: Denney
authors.forename: H M
authors.initials: HM
authors.lastname: McConnell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005470:Fluorometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D018448:Models, Immunological; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein