title: pH dependence and exchange of high and low responder peptides binding to a class II MHC molecule.
abstract: We have compared the binding kinetics of two antigenic peptides to a soluble class II MHC molecule. One of the peptides provokes a strong T cell response and the other a much weaker one. Both show greatly increased (approximately 40-fold) association rates at pH 5 in comparison to neutral pH, consistent with the low pH environment of late endosomes being most conducive to class II MHC--peptide binding. Interestingly, the weak peptide has a much faster off-rate that is significantly increased at pH 5 and it can be entirely replaced in an exchange reaction by the stronger one. This suggests that one characteristic of immunodominant peptides is that of nearly irreversible binding, such that they will be strongly selected for in the course of class II MHC transit and recycling through endosomal compartments. Modelling the parameters of this peptide exchange also suggests that a large fraction of the GPI-chimeric MHC molecules used in this study are 'empty' with respect to endogenous peptides, or else occupied with extremely weak ones, consistent with their inability to load processed peptides intracellularly.
authors.affiliation: Howard Hughes Medical Institute, Stanford, CA.
authors.forename: P A
authors.initials: PA
authors.lastname: Reay
authors.forename: D A
authors.initials: DA
authors.lastname: Wettstein
authors.forename: M M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002678:Chimera; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007106:Immune Sera; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007106:Immune Sera; D010455:Peptides; D010738:Type C Phospholipases