The Biogenesis of the MHC Class II Compartment in Human I-Cell Disease B Lymphoblasts

• Published in: The Journal of cell biology 1996-03, Vol.132 (5), p.769-785
• Main Authors: Glickman, Jonathan N., Morton, Phillip A., Slot, Jan W., Kornfeld, Stuart, Geuze, Hans J.
• Format: Article
• Language: English
• Subjects: Antigens; Antigens, Differentiation, B-Lymphocyte - metabolism; B lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - ultrastructure; Biological Transport; Cathepsin D - isolation & purification; Cathepsin D - metabolism; Cell Compartmentation; Cell Line; Cell lines; Cell membranes; Cells; Cellular biology; Clathrin - metabolism; Coated Vesicles - metabolism; Disease; Endocytosis; Enzymes; Glycoproteins - metabolism; Golgi Apparatus - metabolism; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - ultrastructure; Histocompatibility Antigens Class II - isolation & purification; Histocompatibility Antigens Class II - metabolism; Humans; Intracellular Membranes - chemistry; Lysosomes; Lysosomes - metabolism; Molecules; Mucolipidoses - immunology; Mucolipidoses - metabolism; Pepsinogens - metabolism; Receptors; T lymphocytes
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.132.5.769

The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules and 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 β 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 can be incorporated into MIICs simultaneously by a Man-6-P-independent process.