The role of the Ia-invariant chain complex in the posttranslational processing and transport of Ia and invariant chain glycoproteins.
The invariant chain (Ii) is a nonpolymorphic glycoprotein that associates with the Ia alpha- and beta-chains of MHC class II Ag during their transport to the cell surface. Although surface expression of Ia can occur in the absence of Ii, it has not been shown whether the intracellular association of Ia and Ii affects the biosynthetic rate or specificity of posttranslational modifications to the individual molecules. Analysis of transfected cell lines carrying either Ia, Ii, or both Ia and Ii demonstrated efficient assembly of alpha-beta whether or not Ii was present. Pulse-chase studies and two-dimensional gel electrophoresis showed that Ii did not affect the addition of Ia N-linked oligosaccharide chains, or the extent or rate of their conversion to the complex form, nor did it affect the sulfation of alpha and beta glycoproteins. Ii also did not affect the rate of Ia synthesis or appearance of Ia at the cell surface. In contrast, Ia dramatically affected the posttranslational modification of Ii. Although invariant chain was modified by addition of fatty acid, N-linked oligosaccharide, and glycosaminoglycan in the absence of Ia, the processing of Ii-linked oligosaccharide into more acidic, terminally glycosylated forms was significantly less when Ia was absent, and although conversion to proteoglycan did occur, the glycosaminoglycan chains were significantly shorter than normal. The disappearance of radiolabel from the 31,000 Da form of Ii was faster when Ia was present, and the processing of Ii was more rapid when it was associated with Ia. Thus, the rate and manner in which Ii enters and passes through the Golgi is critically affected by Ia.
Simonis
S
S
Department of Microbiology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Miller
J
J
Cullen
S E
SE
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001692:Biological Transport; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011499:Protein Processing, Post-Translational; D013431:Sulfates / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D013431:Sulfates; C045084:invariant chain