Rapid intracellular pathway gives rise to cell surface expression of the MHC class II-associated invariant chain (CD74).
In previous investigations, it had been shown that class II and associated invariant polypeptides are sorted to an endocytic route where transport is delayed. Invariant chain (Ii) is degraded in a post-Golgi compartment, presumably an endosomal vesicle, and only class II molecules emerge on the cell surface. By using a mAb against the extracytoplasmic domain of human Ii, we demonstrate, by electron microscopy and by cytofluorometry, surface expression of Ii on lymphoma cells and on human B lymphocytes. We examined surface expression of Ii upon inhibition by brefeldin A of intracellular transport from the endoplasmic reticulum to the Golgi stack. This treatment rapidly depletes the cell surface of Ii. In the subsequent absence of brefeldin A, Ii appears rapidly at the cell surface. Within 5 h, the previous level of surface Ii (sIi) is reconstituted. Chloroquine abrogates depletion of sIi by brefeldin A, apparently by inhibition of internalization of sIi. Because on its route to the cell surface Ii is not proteolytically digested, it was possible that Ii and associated class II molecules are not separated on this pathway. Immunochemical studies reveal that on the cell surface of a B lymphoma cell line a proportion of Ii and class II polypeptides are associated.
Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.
N
N
Koch
G
G
Moldenhauer
W J
WJ
Hofmann
P
P
Möller
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis*; D001692:Biological Transport; D020126:Brefeldin A; D002738:Chloroquine / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000502:physiology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology; D016253:Microscopy, Immunoelectron; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D003517:Cyclopentanes; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D020126:Brefeldin A; D002738:Chloroquine