H2-O inhibits presentation of bacterial superantigens, but not endogenous self antigens

J Immunol. 2001 Aug 1;167(3):1371-8. doi: 10.4049/jimmunol.167.3.1371.

Abstract

H2-O/HLA-DO are MHC class II accessory molecules that modulate exogenous Ag presentation. Most class II accessory molecules are expressed in all professional APC; however, H2-O is only expressed in B cells and medullary thymic epithelial cells. Because B cells present exogenous Ags and superantigens (SAgs), and medullary thymic epithelial cells are specialized APC for self Ags during negative selection in the thymus, we have hypothesized that H2-O might play a role in MHC class II-restricted SAg and self Ag presentation. In this study, we demonstrate that H2-O expression inhibits presentation of the bacterial SAgs staphylococcal enterotoxins A and B to four SAg-reactive T hybridoma cells. In contrast, H2-O has no effect on presentation of endogenous self Ags, as measured by tumorigenicity in vivo and Ag presentation to three self Ag-specific T hybridoma cells. Additional experiments suggest that H2-O inhibits presentation of exogenous Ags by both newly synthesized and recycling MHC class II molecules. These data suggest H2-O may have a physiological role in tolerance induction and SAg-mediated toxic shock.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology*
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Autoantigens / immunology
  • Autoantigens / metabolism*
  • Binding, Competitive / immunology
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Enterotoxins / immunology
  • Enterotoxins / metabolism*
  • Female
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / metabolism
  • Histocompatibility Antigens Class II / physiology*
  • Immune Tolerance*
  • Male
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Protein Binding / immunology
  • Staphylococcus aureus / immunology
  • Superantigens / immunology
  • Superantigens / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / microbiology
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antigens, Bacterial
  • Antigens, Neoplasm
  • Autoantigens
  • Enterotoxins
  • H-2O antigen
  • Histocompatibility Antigens Class II
  • Superantigens
  • enterotoxin B, staphylococcal