Quality control of MHC class II associated peptides by HLA-DM/H2-M

For many years the crucial components involved in MHC class II mediated ant igen presentation have been thought to be known: polymorphic MHC class II m olecules, the monomorphic invariant chain (li) and a set of conventional pr oteases that cleave antigenic proteins thereby generating ligands able to a ssociate with MHC class II molecules. However; in 1994 if was found that wi thout an additional molecule, HLA-DM (DM), efficient presentation of protei n antigens cannot be achieved. Biochemical Studies showed that DM acts as a molecular chaperone protecting empty MHC class II molecules from functiona l inactivation. In addition, it serves as a peptide editor: DM catalyzes no t only the release of the invariant chain remnant CLIP, but of all sorts of low-stability peptides, and simultaneously favours binding of high-stablit y peptides. Through this quality control of peptide loading, DM enables APC s to optimize MHC restriction and to display their antigenic peptide cargo on the surface from prolonged periods of time to be scrutinized by T cells.