title: Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells.
abstract: Dendritic cells (DCs) developmentally regulate their capacity for antigen presentation by controlling the transport and surface expression of MHC class II molecules. These events reflect a developmental regulation of invariant (Ii) chain cleavage, most likely by the cysteine protease cathepsin S. In immature DCs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the transport of class II-Ii chain complexes to lysosomes, while in mature DCs, elevated cathepsin S activity results in efficient delivery of class II alphabeta dimers to the plasma membrane. Cathepsin S is not controlled transcriptionally but by a novel mechanism involving alterations in the expression and localization of an endogenous cathepsin S inhibitor cystatin C. Thus, the ratio of cystatin C to cathepsin S in developing DCs helps to determine the fate of newly synthesized MHC class II molecules.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA.
authors.forename: P
authors.initials: P
authors.lastname: Pierre
authors.forename: I
authors.initials: I
authors.lastname: Mellman
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001692:Biological Transport; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis / Q000235:genetics; D018076:DNA, Complementary; D003713:Dendritic Cells / Q000276:immunology*; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D014162:Transfection
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D002403:Cathepsins; C028217:cathepsin S