Cathepsin S required for normal MHC class II peptide loading and germinal center development

Immunity. 1999 Feb;10(2):197-206. doi: 10.1016/s1074-7613(00)80020-5.


Major histocompatibility complex (MHC) class II molecules acquire antigenic peptides after degradation of the invariant chain (Ii), an MHC class II-associated protein that otherwise blocks peptide binding. Antigen-presenting cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10 kDa fragment, resulting in delayed peptide loading and accumulation of cell surface MHC class II/10 kDa Ii complexes. Although cathepsin S-deficient mice have normal numbers of B and T cells and normal IgE responses, they show markedly impaired antibody class switching to IgG2a and IgG3. These results indicate cathepsin S is a major Ii-processing enzyme in splenocytes and dendritic cells. Its role in humoral immunity critically depends on how antigens access the immune system.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation
  • Antigen Presentation
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Cathepsins / physiology*
  • Chimera
  • Dendritic Cells / immunology
  • Freund's Adjuvant / immunology
  • Germinal Center / physiology*
  • Histocompatibility Antigens Class II / metabolism*
  • Immunization
  • Immunoglobulin Class Switching
  • Mice
  • Mice, Mutant Strains
  • Peptides / metabolism*
  • Spleen / immunology


  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Peptides
  • invariant chain
  • Freund's Adjuvant
  • Cathepsins
  • cathepsin S