In vivo control of endosomal architecture by class II-associated invariant chain and cathepsin S.
The invariant chain (Ii) is a chaperone that regulates assembly and transport of class II MHC molecules. In the absence of the lysosomal protease cathepsin S (CatS), degradation of Ii is impaired and an Ii remnant that extends from the N terminus to about residue 110 accumulates in class II MHC-positive endosomal compartments, which are enlarged in size and lack multivesicular morphology. In primary B cells examined in vitro and in lymph nodes examined by immuno-electron microscopy, CatS controls architecture of class II-positive endosomal compartments. In a compound mutant mouse that lacks both CatS and Ii, the normal size of endosomes in class II-positive cells is restored, although internal endosomal membranes are absent. Proper degradation of Ii is thus essential for normal endosomal morphology in antigen-presenting cells in vivo.
Boes
Marianne
M
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. mboes@rics.bwh.harvard.edu
van der Wel
Nicole
N
Peperzak
Victor
V
Kim
You-Me
YM
Peters
Peter J
PJ
Ploegh
Hidde
H
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002403:Cathepsins / Q000172:deficiency / Q000276:immunology*; D002451:Cell Compartmentation / Q000276:immunology; D011992:Endosomes / Q000201:enzymology* / Q000276:immunology* / Q000648:ultrastructure; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; C045084:invariant chain; D002403:Cathepsins; C028217:cathepsin S