title: A toxic shock syndrome toxin 1 mutant that defines a functional site critical for T-cell activation.
abstract: Toxic shock syndrome toxin 1 (TSST-1), a superantigen produced by Staphylococcus aureus, is a causative agent of toxic shock syndrome (TSS). This superantigen is a potent stimulator of T cells and macrophages/monocytes, resulting in the release of cytokines that are implicated in the pathogenesis of TSS. This study characterizes a mutant TSST-1, derived by site-directed mutagenesis, that has an alanine substitution at histidine 135 (mutant 135). This single-amino-acid change results in a mutant toxin that has lost mitogenic activity for T cells. In contrast to wild-type TSST-1, this mutant does not induce T cells to express interleukin-2, gamma interferon, or tumor necrosis factor beta (TNF-beta). The inability of mutant 135 to activate T cells is not due to a lack of binding to the class II major histocompatibility complex receptor. In addition, the mutant TSST-1 does not induce expression of TNF-alpha, which plays a role in the development of lethal shock. The lack of TNF-alpha induction by mutant 135 is likely due to its inability to activate T cells. These data suggest that the mutation at histidine 135 in TSST-1 affects toxin interactions with the T-cell receptor rather than the class II major histocompatibility complex receptor.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Cullen
authors.forename: L R
authors.initials: LR
authors.lastname: Blanco
authors.forename: P F
authors.initials: PF
authors.lastname: Bonventre
authors.forename: E
authors.initials: E
authors.lastname: Choi
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D001483:Base Sequence; D004768:Enterotoxins / Q000737:chemistry / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D007371:Interferon-gamma