Endosomal proteases in antigen presentation

Processing of cytoplasmic and endocytized foreign antigens were once thought to be completely separate pathways of peptide generation for MHC class I and class II peptide display. However, recent studies show actually that there is extensive overlap owing, in part, to the positioning of endosomal proteases at sites in which MHC class I and class II paths cross. The questions of how antigens access and persist at sites of endosomal processing are proving to be as important as those regarding the proteases themselves. However, individual proteases within the set of endosomal enzymes have emerged both as targets for microbial evasion from MHC-class-II-dependent immunity and as required elements in autoimmunity. Repeated implication of cathepsins in processing medically important antigens holds promise for therapeutic manipulation of proteases in diseases in which there is disordered adaptive immunity.