T lymphocyte activation by staphylococcal enterotoxins: Role of class II molecules and T cell surface structures

Fleischer, Bernhard; Schrezenmeier, Hubert; Conradt, Peter

doi:10.1016/0008-8749(89)90177-9

Cited by 84 publications

(49 citation statements)

References 19 publications

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“…White et al [15] and Fleischer et al [16] demonstrated that T cell response to SEA are not MHC class II restricted and that mouse TCR can recognize non host APC expressing MHC class II alleles from different species. However, these authors did not take into consideration that CD4 + T cells that express MHC class II molecules on their cell surface can act as APCs.…”

Section: Discussionmentioning

confidence: 99%

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Rasooly¹,

Paula²,

Hernlem³

2011

OJI

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Section: Discussionmentioning

confidence: 99%

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Rasooly¹,

Paula²,

Hernlem³

2011

OJI

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“…The disease is characterized by fever, hypotension, desquamation of skin, and dysfunction of multiple organ systems (8,38,41). These toxins bind directly to the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and subsequently stimulate T cells expressing specific V␤ elements on T-cell receptors (9,15,24,29,35,42). Staphylococcal enterotoxin B (SEB) and the distantly related toxic shock syndrome toxin 1 are also called superantigens because they induce massive proliferation of T cells (29).…”

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confidence: 99%

Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine ReleaseInVitroandIn Vivo

Krakauer

Buckley

Issaq

et al. 2010

Antimicrob Agents Chemother

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Staphylococcal enterotoxins are potent activators for human T cells and cause lethal toxic shock. Rapamycin, an immunosuppressant, was tested for its ability to inhibit staphylococcal enterotoxin B (SEB)-induced activation of human peripheral blood mononuclear cells (PBMC) in vitro and toxin-mediated shock in mice. Stimulation of PMBC by SEB was effectively blocked by rapamycin as evidenced by the inhibition of tumor necrosis factor alpha (TNF-␣), interleukin 1␤ (IL-1␤), IL-6, IL-2, gamma interferon (IFN-␥), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1␣ (MIP-1␣), MIP-1␤, and T-cell proliferation. In vivo, rapamycin protected 100% of mice from lethal shock, even when administered 24 h after intranasal SEB challenge. The serum levels of MCP-1 and IL-6, after intranasal exposure to SEB, were significantly reduced in mice given rapamycin versus controls. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB.Staphylococcal exotoxins are among the most common etiological agents that cause toxic shock syndrome (28-30, 38, 44). The disease is characterized by fever, hypotension, desquamation of skin, and dysfunction of multiple organ systems (8,38,41). These toxins bind directly to the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and subsequently stimulate T cells expressing specific V␤ elements on T-cell receptors (9,15,24,29,35,42). Staphylococcal enterotoxin B (SEB) and the distantly related toxic shock syndrome toxin 1 are also called superantigens because they induce massive proliferation of T cells (29). In vitro and in vivo studies show that these superantigens induce high levels of various proinflammatory cytokines, and these potent mediators cause lethal shock in animal models (1,6,22,27,37,39,45,51,55). SEB also causes food poisoning (4, 21, 52) and is a potential bioterrorism threat agent, as humans are extremely sensitive to this superantigen, especially by inhalation (28). There is currently no effective therapeutic treatment for SEB-induced shock except for the use of intravenous immunoglobulins (11). Various in vitro experiments identified inhibitors to counteract the biological effects of SEB, only some of which were successful in ameliorating SEB-induced shock in experimental models (1,(25)(26)(27)51).Rapamycin is a relatively new FDA-approved drug used to prevent graft rejection in renal transplantation, as it shows less nephrotoxicity than do calcineurin inhibitors (14,40,43,48). Recent studies reveal other uses in animal models of cancer (23, 34), diabetic nephropathy (36), bleomycin-induced pulmonary fibrosis (31), liver fibrosis (5), and tuberous sclerosis (32). Rapamycin binds intracellularly to FK506-binding proteins, specifically FKBP12; the rapamycin-FKBP12 complex then binds to a distinct molecular target called mammalian target of rapamycin (mTOR) (reviewed in reference 48). Rapamycin inhibits mTOR activity, prevents cyclin-dependent kinase activation, and affects G 1 -to-S-pha...

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“…Superantigen binding to major histocompatibility complex (MHC) class II molecules is a prerequisite for T-cell stimulation (2,(12)(13)(14) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

Section: Introductionmentioning

confidence: 99%

“…Superantigen binding to major histocompatibility complex (MHC) class II molecules is a prerequisite for T-cell stimulation (2,(12)(13)(14). The binding of conventional peptide antigens to MHC class II has been well-documented (15)(16)(17)(18)(19); however, little is known about the site for superantigen binding.…”

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confidence: 99%

“…The superantigen family includes mouse self superantigens encoded by mouse mammary tumor viruses (6-8) and a number of microbial exotoxins implicated in severe shock-like disorders. Among the best characterized superantigens are the staphylococcal exotoxins, a family of basic secretory proteins of 22-30 kDa such as the staphylococcal enterotoxins (SEs) SEA, SEB, SEC1-3, SED, and SEE and the toxic shock syndrome toxin (9-11).Superantigen binding to major histocompatibility complex (MHC) class II molecules is a prerequisite for T-cell stimulation (2,(12)(13)(14) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

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Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR.

Herman

Labrecque

Thibodeau

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

102

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The staphylococcal enterotoxin A (SEA) is a superantigen that must bind to class II molecules of the major histocompatibility complex to be recognized by T cells. In humans, most HLA-DR class II allelic and isotypic forms, such as DR1, bind SEA well. DRw53 is an exception, binding SEA very poorly. We have localized this difference to a single residue (amino acid 81) in the fl1 domain. A highly conserved histidine at residue 81 allows SEA binding, but a tyrosine does not. Residue 81 is predicted to lie in an a-helix on the surface of the molecule, with its side chain pointing up out of the pocket associated with binding of conventional peptide antigens. This rinding supports the hypothesis that superantigens and conventional antigens bind to different sites on the class II molecule.Recently, a class of antigens has been characterized that stimulates T cells predominantly through the 13chain variable region element of the T-cell receptor (1-3). They differ from conventional peptide antigens, which require specific interaction with several variable elements of the T-cell receptor (4, 5). These molecules have been termed superantigens, since they stimulate large numbers of T cells (2). The superantigen family includes mouse self superantigens encoded by mouse mammary tumor viruses (6-8) and a number of microbial exotoxins implicated in severe shock-like disorders. Among the best characterized superantigens are the staphylococcal exotoxins, a family of basic secretory proteins of 22-30 kDa such as the staphylococcal enterotoxins (SEs) SEA, SEB, SEC1-3, SED, and SEE and the toxic shock syndrome toxin (9-11).Superantigen binding to major histocompatibility complex (MHC) class II molecules is a prerequisite for T-cell stimulation (2,(12)(13)(14) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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T lymphocyte activation by staphylococcal enterotoxins: Role of class II molecules and T cell surface structures

Cited by 84 publications

References 19 publications

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine ReleaseInVitroandIn Vivo

Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR.

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T lymphocyte activation by staphylococcal enterotoxins: Role of class II molecules and T cell surface structures

Cited by 84 publications

References 19 publications

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4&lt;sup&gt;+&lt;/sup&gt; T cells

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4&lt;sup&gt;+&lt;/sup&gt; T cells

Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine ReleaseInVitroandIn Vivo

Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR.

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Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells