title: Staphylococcal enterotoxin A and toxic shock syndrome toxin compete with CD4 for human major histocompatibility complex class II binding.
abstract: We have examined the role of the CD4 molecule in primary T-lymphocyte responses to the staphylococcal enterotoxins SEA, SEB, SEC1, and the toxic shock syndrome toxin TSST-1. Proliferating cells were predominantly CD4+; however, the responses to SEA and TSST-1 were most sensitive to inhibition by the anti-CD4 antibody Leu-3a. T-lymphocyte responses to the bacterial superantigens were inhibited by site-directed mutations of residues in the DR beta membrane-proximal domain (DR beta 2) that are also known to be important for interactions with CD4. SEA and TSST-1 binding to DR was reduced by the DR beta 2 mutations and by competition with soluble recombinant CD4. We propose that bacterial superantigens sequentially, or simultaneously with CD4, stabilize complexes of T-cell antigen receptors and major histocompatibility complex class II molecules. The superantigen qualities of these toxins may be due, in part, to a molecular mimicry of CD4 and other adhesion molecules.
authors: Department of Immunology and Molecular Biology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011.
authors: S
authors: S
authors: Bavari
authors: R G
authors: RG
authors: Ulrich
mesh_terms: D001427:Bacterial Toxins; D001665:Binding Sites; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004768:Enterotoxins / Q000378:metabolism*; D006681:HLA-D Antigens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D018089:Superantigens / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D015704:CD4 Antigens; D004768:Enterotoxins; D006681:HLA-D Antigens; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; C034959:enterotoxin C, staphylococcal