X-ray crystallographic analysis has shown that CLIP sits in the peptide-binding cleft in the same way that other peptides bind to class II MHC molecules.
Therefore, removal of CLIP is required before the cleft becomes accessible to peptides produced from extracellular proteins.
This is accomplished by the ac ion of a molecule called HLA-DM (or H-2M in the mouse), which is
encoded within the MHC, has a structure similar to that of class II MHC molecules, and colocalizes with class II molecules in the MIIC compartment.
HLA-DM molecules differ from class II MHC molecules in several respects: they are not polymorphic, they do not associate with the Ii, and they are not expressed on the cell surface.
HLA-DM acts as a peptide exchanger facilitating the removal of CLIP and the addition of other peptides to class II MHC molecules.