Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells.
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.
Pierre
P
P
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA.
Mellman
I
I
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
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