Cutting edge: Editing of recycling class II: Peptide complexes by HLA-DM

HLA-DM catalyzes the exchange and selection of ligands for MHC class II mol ecules within mature endosomal/lysosomal compartments. Here, evidence is pr ovided that DM edits peptides in early endosomes, thus influencing presenta tion via recycling class II molecules. Maximal class H-restricted presentat ion of an albumin-derived peptide, dependent on endocytosis and recycling c lass II molecules, was observed in cells lacking HLA-DM. DM editing of this epitope was observed in early endocytic compartments as shown using inhibi tors of early to late endosomal transport. Editing was tempered by coexpres sion of HLA-DO, suggesting that DM:DO ratio may be important in guiding epi tope editing in early endosomal compartments. Thus, HLA-DM appears to inter act with, and edit epitopes displayed by, recycling class II molecules.