The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway.

HLA-DM serves a critical function in the loading and editing of peptides on MHC class II (MHCII) molecules. Recent data showed that the interaction cycle between MHCII molecules and HLA-DM is dependent on the occupancy state of the peptide binding groove. Empty MHCII molecules form stable complexes with HLA-DM, which are disrupted by binding of high-affinity peptide. Interestingly, MHCII molecules with fully engaged peptides cannot interact with HLA-DM, and prior dissociation of the peptide N-terminus from the groove is required for HLA-DM binding. There are significant similarities to the peptide loading process for MHC class I molecules, even though it is executed by a distinct set of proteins in a different cellular compartment. Copyright Â