Invariant chain controls H2-M proteolysis in mouse splenocytes and dendritic cells

J Exp Med. 2000 Mar 20;191(6):1057-62. doi: 10.1084/jem.191.6.1057.

Abstract

The association of invariant (Ii) chain with major histocompatibility complex (MHC) class II dimers is required for proper antigen presentation to T cells by antigen-presenting cells. Mice lacking Ii chain have severe abnormalities in class II transport, T cell selection, and B cell maturation. We demonstrate here that H2-M, which is required for efficient class II antigenic peptide loading, is unexpectedly downregulated in splenocytes and mature dendritic cells (DCs) from Ii(-/-) mice. Downregulation reflects an increased rate of degradation in Ii(-/-) cells. Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin. Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, Differentiation, B-Lymphocyte / biosynthesis
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • Cells, Cultured
  • Chemical Precipitation
  • Cytosol / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Endopeptidases / metabolism*
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • HLA-D Antigens / genetics
  • HLA-D Antigens / isolation & purification
  • HLA-D Antigens / metabolism*
  • Half-Life
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Histocompatibility Antigens Class II / physiology*
  • Hydrolysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Folding
  • RNA, Messenger / metabolism
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / metabolism*

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • H2-M antigens
  • HLA-D Antigens
  • HLA-DM antigens
  • Histocompatibility Antigens Class II
  • RNA, Messenger
  • invariant chain
  • Endopeptidases