Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice

Immunity. 1999 Feb;10(2):207-17. doi: 10.1016/s1074-7613(00)80021-7.

Abstract

Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of invariant chain (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii degradation in professional APC in vivo. A marked variation in the generation of MHC class II-bound Ii fragments and presentation of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibility to collagen-induced arthritis, suggesting a potential therapeutic target for regulation of immune responsiveness.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Arthritis / chemically induced
  • Arthritis / immunology*
  • Cathepsins / genetics
  • Cathepsins / physiology*
  • Collagen
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Drug Design
  • Gene Targeting
  • Histocompatibility Antigens Class II / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Spleen / immunology
  • Spleen / metabolism

Substances

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