HLA-DO expands the repertoire of peptides presented by class II MHC molecules such as HLA-DR. (Top) In the MIIC, HLA-DM facilitates the exchange of CLIP for specific DM-resistant peptides into the binding groove of class II molecules, which are then transported to the cell surface. The loading of DM-sensitive antigens is inhibited. (Bottom) In the presence of HLA-DO, both DM-resistant and DM-sensitive antigens are loaded, leading to a more diverse repertoire of peptide/class II MHC molecules displayed on the cell surface. Professional illustration by Debra T. Dartez.