Protein degradation in MHC class II antigen presentation: opportunities for immunomodulation

Proteolysis is required for two steps of the MHC class II antigen-processin g pathway, degradation of invariant chain and cleavage of protein antigens. Invariant chain dissociation from MHC is limited by a final proteolytic ev ent which is tightly regulated in both temporal and tissue-specific ways. I n contrast, enzymes involved in antigen proteolysis remain ill-defined Gene 'knockout' experiments of housekeeping proteolytic enzymes suggest either that these enzymes do not play a major role, or that antigen proteolysis is too degenerate for this type of analysis. The possible role of two other p roteinases, cathepsin E and aspariginyl endopeptidase is discussed. Finally , the data implicating antigen processing in repertoire generation is brief ly considered. We conclude that selective regulation of endosomal proteolys is could have profound implications for control of immunity against infecti on, as well as in autoimmunity.