Processing and regulation mechanisms within antigen presenting cells: a possibility for therapeutic modulation

Processing of antigens within antigen presenting cells (APCs) is necessary for an immune response. Two pathways exist to present antigens to T cells: the major histocompatibility complex class I (MHC I) pathway to activate cytotoxic T cells (CTLs) and the MHC II route to stimulate T helper cells (Ths). Prior to efficient antigen presentation to MHC II, antigens have to be proteolytically degraded by proteases, the cathepsins, inside the endocytic compartment of APCs. Cathepsins process both antigens and self-antigens to antigenic peptides; the latter are critical for autoimmunity. Remarkably, distribution, substrate specificity, and function of cathepsins located in the antigen processing machinery depend on the cell type, primary or cultured cells, or species analyzed. However, a precise understanding of the antigen processing and presentation machinery is needed to generate specific immune modulators since the MHC antigen- processing pathway is subsequently regulated during tumorigenesis, infection, or autoimmunity. In this review, the latest finding regarding function and regulation of the MHC II proteolytic machinery and its possible target for immunomodulation will be discussed.