In vivo control of endosomal architecture by class II-associated invariant chain and cathepsin S

Eur J Immunol. 2005 Sep;35(9):2552-62. doi: 10.1002/eji.200526323.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cathepsins / deficiency
  • Cathepsins / immunology*
  • Cell Compartmentation / immunology
  • Endosomes / enzymology*
  • Endosomes / immunology*
  • Endosomes / ultrastructure
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / immunology*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Specific Pathogen-Free Organisms
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Lipopolysaccharides
  • invariant chain
  • Cathepsins
  • cathepsin S