H2-O inhibits presentation of bacterial superantigens, but not endogenous self antigens.
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.
Qi
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Department of Biological Sciences, University of Maryland, Baltimore, MD 21250.
Ostrand-Rosenberg
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D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D000951:Antigens, Neoplasm; D001324:Autoantigens; D004768:Enterotoxins; C416186:H-2O antigen; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C031818:enterotoxin B, staphylococcal