Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules.
Toxic shock syndrome toxin 1 (TSST-1) is a 22-kDa exotoxin produced by strains of Staphylococcus aureus and implicated in the pathogenesis of toxic shock syndrome. In common with other staphylococcal exotoxins, TSST-1 has diverse immunological effects. These include the induction of interleukin 2 receptor expression, interleukin 2 synthesis, proliferation of human T lymphocytes, and stimulation of interleukin 1 synthesis by human monocytes. In the present study, we demonstrate that TSST-1 binds with saturation kinetics and with a dissociation constant of 17-43 nM to a single class of binding sites on human mononuclear cells. There was a strong correlation between the number of TSST-1 binding sites and the expression of major histocompatibility complex class II molecules, and interferon-gamma induced the expression of class II molecules as well as TSST-1 binding sites on human skin-derived fibroblasts. Monoclonal antibodies to HLA-DR, but not to HLA-DP or HLA-DQ, strongly inhibited TSST-1 binding. Affinity chromatography of 125I-labeled cell membranes over TSST-1-agarose resulted in the recovery of two bands of 35 kDa and 31 kDa that comigrated, respectively, with the alpha and beta chains of HLA-DR and that could be immunoprecipitated with anti-HLA-DR monoclonal antibodies. Binding of TSST-1 was demonstrated to HLA-DR and HLA-DQ L-cell transfectants. These results indicate that major histocompatibility complex class II molecules represent the major binding site for TSST-1 on human cells.
Scholl
P
P
Division of Allergy and Immunology, Children's Hospital, Boston, MA.
Diez
A
A
Mourad
W
W
Parsonnet
J
J
Geha
R S
RS
Chatila
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001427:Bacterial Toxins; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D007739:L Cells / Q000276:immunology; D051379:Mice; D011485:Protein Binding; D011956:Receptors, Cell Surface; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D011956:Receptors, Cell Surface; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal