Inhibition of staphylococcal enterotoxin A-induced superantigenic and lethal activities by a monoclonal antibody to toxic shock syndrome toxin-1.
Staphylococcal toxic shock syndrome is caused by a family of related superantigens that includes toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins (SEs) A, B, and C. The cross-inhibitory activity against SEA by a novel anti-TSST-1 monoclonal antibody (MAb), MAb5, which also cross-inhibits SEB-induced superantigenic activities, was investigated. MAb5 blocked SEA binding to human monocytes, cross-neutralized SEA-induced T cell mitogenesis and TNF-alpha secretion in human peripheral blood mononuclear cells, and prevented lethality in mice. Epitope mapping revealed that MAb5 binds to residues SEA(154-161) within the central alpha helix that is structurally highly conserved among TSST-1, SEA, and SEB. The cross-inhibitory activity of MAb5 is likely due to steric hindrance of this conserved motif, although the precise function of this motif shared among related staphylococcal superantigens remains to be further elucidated.
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Department of Medicine and Microbiology, Division of Infectious Diseases, University of British Columbia, and Vancouver Hospital Health Sciences Centre, Vancouver, Canada.
Chow
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D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007369:Interferon Inducers / Q000037:antagonists & inhibitors / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D007369:Interferon Inducers; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal