Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells

Cell. 1998 Jun 26;93(7):1135-45. doi: 10.1016/s0092-8674(00)81458-0.

Abstract

Dendritic cells (DCs) developmentally regulate their capacity for antigen presentation by controlling the transport and surface expression of MHC class II molecules. These events reflect a developmental regulation of invariant (Ii) chain cleavage, most likely by the cysteine protease cathepsin S. In immature DCs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the transport of class II-Ii chain complexes to lysosomes, while in mature DCs, elevated cathepsin S activity results in efficient delivery of class II alphabeta dimers to the plasma membrane. Cathepsin S is not controlled transcriptionally but by a novel mechanism involving alterations in the expression and localization of an endogenous cathepsin S inhibitor cystatin C. Thus, the ratio of cystatin C to cathepsin S in developing DCs helps to determine the fate of newly synthesized MHC class II molecules.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / physiology
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Biological Transport
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism
  • Cell Membrane / metabolism
  • Cystatin C
  • Cystatins / analysis
  • Cystatins / genetics
  • Cysteine Proteinase Inhibitors / analysis
  • Cysteine Proteinase Inhibitors / genetics
  • DNA, Complementary
  • Dendritic Cells / immunology*
  • Dimerization
  • Enzyme Inhibitors / pharmacology
  • Histocompatibility Antigens Class II / metabolism*
  • Lysosomes / metabolism
  • Male
  • Mice
  • Transfection

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Cst3 protein, mouse
  • Cystatin C
  • Cystatins
  • Cysteine Proteinase Inhibitors
  • DNA, Complementary
  • Enzyme Inhibitors
  • Histocompatibility Antigens Class II
  • invariant chain
  • Cathepsins
  • cathepsin S