Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion.
The mechanism of how superantigens function to activate cells has been linked to their ability to bind and cross-link the major histocompatibility complex class II (MHCII) molecule. Cells that lack the MHCII molecule also respond to superantigens, however, with much less efficiency. Therefore, the purpose of this study was to confirm that staphylococcal enterotoxin A (SEA) could bind the MHCI molecule and to test the hypothesis that cross-linking SEA bound to MHCII-deficient macrophages would induce a more robust cytokine response than without cross-linking. We used a capture enzyme-linked immunosorbent assay and an immunprecipitation assay to directly demonstrate that MHCI molecules bind SEA. Directly cross-linking MHCI using monoclonal antibodies or cross-linking bound SEA with an anti-SEA antibody or biotinylated SEA with avidin increased TNF-alpha and IL-6 secretion by MHCII(-/-) macrophages. The induction of a vigorous macrophage cytokine response by SEA/anti-SEA cross-linking of MHCI offers a mechanism to explain how MHCI could play an important role in superantigen-mediated pathogenesis.
Wright
A D
AD
Division of Biology, Kansas State University, Manhattan, Kansas 66506, USA.
Chapes
S K
SK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004768:Enterotoxins / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D004768:Enterotoxins; D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal