The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts.
The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules nd lysosomal hydrolases were studied in I-Cell Disease (ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC class II-invariant chain complexes colocalized with the lysosomal hydrolase cathepsin D in buds and vesicles that lacked markers of clathrin-coated vesicle-mediated transport. These vesicles fused with the endocytic pathway leading to the formation of "early" MHC class II-rich compartments (MIICs). Similar structures were observed in the TGN of normal beta lymphoblasts although they were less abundant. Metabolic labeling and subcellular fractionation experiments indicated that newly synthesized cathepsin D and MHC class II-invariant chain complexes enter a non-clathrin-coated vesicular structure after their passage through the TGN and segregation from the secretory pathway. These vesicles were also devoid of the cation-dependent mannose 6-phosphate (Man-6-P) receptor, a marker of early and late endosomes. These findings suggest that in ICD B lymphoblasts the majority of MHC class II molecules are transported directly from the TGN to "early" MIICs and that acid hydrolases cam be incorporated into MIICs simultaneously by a Man-6-P-independant process.
Glickman
J N
JN
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Morton
P A
PA
Slot
J W
JW
Kornfeld
S
S
Geuze
H J
HJ
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D002402:Cathepsin D / Q000302:isolation & purification / Q000378:metabolism; D002451:Cell Compartmentation; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D018699:Coated Vesicles / Q000378:metabolism; D004705:Endocytosis; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D000949:Histocompatibility Antigens Class II / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry; D008247:Lysosomes / Q000378:metabolism; D009081:Mucolipidoses / Q000276:immunology / Q000378:metabolism*; D010435:Pepsinogens / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D002966:Clathrin; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D010435:Pepsinogens; C045084:invariant chain; D002402:Cathepsin D