Figure 9. A model for the effects of HLA-DO on antigen presentation.

DO likely interacts with peptide-receptive DR molecules and may stabilize an overly receptive conformation. This conformation lends itself to a more efficient release of the poorly binding peptides while helping the formation of compact complexes with the well-fitting peptides. In the pool of available peptides those with weak anchoring residues that tend to be more DM-sensitive may not get a chance to stabilize in the groove, and therefore are outcompeted by DM-resistant peptides with bulkier hydrophobic P1 pocket residues. We theorize that DO interacts primarily with DR molecules in receptive conformation mostly generated by the effector function of DM.