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

► DM and MHCII molecules form stable complexes in the absence of peptide. ► Peptide binding induces dissociation of DM from MHCII. ► MHCII molecules with fully bound peptides do not interact with DM. ► Dissociation of the peptide N-terminus from the MHC groove is required for DM binding. ► Key principles of peptide loading are similar between MHC class I and II molecules.