KINETICS OF THE REACTIONS BETWEEN THE INVARIANT CHAIN (85-99) PEPTIDEAND PROTEINS OF THE MURINE CLASS-II MHC

The region comprising residues 83-107 of the extracytoplasmic domain o f the class II MHC-associated invariant chain protein is essential for its functional interaction with MHC proteins. A nested set of peptide s that encompass this region, designated the class II invariant chain- derived peptides (CLIP), bind to many MHC proteins and inhibit the bin ding of antigenic peptides, The kinetics of the reactions between CUP and five different murine class ii MHC proteins have been determined, specificity of CLIP binding was confirmed by competition with antigeni c peptides, Large differences in the reaction rates were observed, For example, half-times of dissociation ranged from 4.4 min to 17.5 h, a > 200-fold difference, These results demonstrate that CLIP bind to MHC heterodimers at a site that involves the polymorphic residues, These data support the hypothesis that the CLIP binding site is within the p eptide binding groove, It is further suggested that these differences in kinetic stabilities of CLIP-MHC protein complexes might affect the diversity of endogenous peptides bound to class II MHC proteins.