Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes. Destructive potential of the aspartyl protease cathepsin D in MHC class II-restricted antigen processing. Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP. Asparaginyl endopeptidase: case history of a class II MHC compartment protease. MHC-guided processing: binding of large antigen fragments. Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival. MIF signal transduction initiated by binding to CD74. This paper shows that the regulation of invariant chain degradation by cathepsin S in DCs controls both MHC class II-restricted antigen presentation and cell migration to lymph nodes. Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain. The cytoplasmic tail of invariant chain regulates endosome fusion and morphology. Uncoating ATPase Hsc70 is recruited by invariant chain and controls the size of endocytic compartments. Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice. Asparagine endopeptidase can initiate the removal of the MHC class II invariant chain chaperone. Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. The lysosomal cysteine proteases in MHC class II antigen presentation. Regulated release of endolysosomal proteases might contribute to leukocyte homeostasis.ĭell'Angelica, E.
Release of proteases from LROs into the host cell cytoplasm can trigger apoptosis unless the proteases are countered by cytoplasmic protease inhibitors. They are released following fusion of the LRO with the plasma membrane and function in the killing of target cells or in immune signalling. The granzyme proteases of cytotoxic T lymphocytes are stored in LROs. Many parasites produce endolysosomal proteases of their own, which are used to facilitate host invasion or subvert the host's immune response. Some pattern recognition receptors, such as the endosomal members of the Toll-like receptor family, TLR7 and TLR9, are activated by endolysosomal proteases. The range of proteases present in LROs is cell-type specific.Įndolysosomal proteolysis can involve relatively non-specific degradation, as in the formation of antigenic peptides by antigen-presenting cells, or precise cleavage events, as in the stepwise degradation of the MHC class II chaperone invariant chain. Lysosome-related organelles (LROs) or granules are the main protease storage and processing organelles of the endolysosomal system. Proteases that are resident in, or released from, the endolysosomal system of leukocytes have important functions in the immune response.