ISOMERIC COMPLEXES OF PEPTIDES WITH CLASS-II PROTEINS OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

An important event in the generation of an immune response is the acti vation of T cells by peptides bound to the class II proteins of the ma jor histocompatiblity complex (MHC). Binding of a peptide to an MHC pr otein is stabilized by multiple interactions between the protein, pept ide side-chains, and peptide backbone. Unstable protein-peptide comple xes that precede formation of long-lived complexes are presumably enga ged in a smaller number of these binding interactions. To investigate the effect of peptide structure on the formation of unstable complexes , we have strategically modified a peptide that forms only long-lived complexes (dissociation rate constant k(off) = 2.5 x 10(-6) s(-1)). Di ssociation of the modified peptide from an MHC protein is biphasic wit h dissociation rate constants k(off) = 5.3 x 10(-4) and 2.6 x 10(-6) s (-1). Thus, at least two detectable complexes are formed. These result s demonstrate that changes in peptide structure alone are sufficient t o result in the formation of isomeric structures of MHC protein-peptid e complexes.