| DM facilitates formation of high affinity complexes of peptide-major histocompatibility complex (MHC) by release of class II MHC-associated invariant chain peptide (CLIP). This has been proposed to occur through discrimination of complex stability. By probing kinetic and conformational intermediates of the wild-type and mutant human histocompatibility leukocyte antigen (HLA)-DR1-peptide complexes, and examining their reactivities with DM, we propose that DM interacts with the flexible hydrophobic pocket 1 of DR1 and converts the molecule into a conformation that is highly peptide receptive. A more rigid conformation, generated upon filling of pocket 1, is less susceptible to DM effects. Thus, DM edits peptide-MHC by recognition of the conformation change upon peptide binding. By superantigen blocking, pocket 1 region of DR1 was shown to play an important role in the interaction between DM and DR1. We are able to show that a helper peptide, AE206, may function similarly with DM through the same mechanism. Homology search among CLIP, DM and AE206, two sequences, PKL(α85–87) and KPL (α106–108), were proposed to interact with DM during peptide exchange. |
