The crystal structure of staphylococcal enterotoxin H: implications for binding properties to MHC class II and TcR molecules

Håkansson, Maria; Petersson, Karin; Nilsson, Helén; Forsberg, G.; Björk, Per; Antonsson, Per; Svensson, L.A.

doi:10.1006/jmbi.2000.4093

Cited by 49 publications

(45 citation statements)

References 57 publications

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“…One interpretation of the cytotoxicity assays as well as competition experiments is that SEH directly interacts with TCR to cause this expansion. The V␣ specificity of SEH contradicts all previously published data on T cell stimulation by superantigens, but SEH still has to be regarded as a bacterial superantigen since it exhibits all other characteristics of the protein family; e.g., like a similar three-dimensional fold (13), the ability to bind MHC class II (21,36), potent T cell mitogen properties (36), and the ability to induce acute toxic shock in mammals (50). A striking difference between SEH and other SEs is, however, the incapability of SEH to induce T cell activation in mice (37).…”

Section: Discussionmentioning

confidence: 63%

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Petersson

Pettersson

Skartved

et al. 2003

The Journal of Immunology

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Staphylococcal enterotoxin H (SEH) is a bacterial superantigen secreted by Staphylococcus aureus. Superantigens are presented on the MHC class II and activate large amounts of T cells by cross-linking APC and T cells. In this study, RT-PCR was used to show that SEH stimulates human T cells via the Vα domain of TCR, in particular Vα10 (TRAV27), while no TCR Vβ-specific expansion was seen. This is in sharp contrast to all other studied bacterial superantigens, which are highly specific for TCR Vβ. It was further confirmed by flow cytometry that SEH stimulation does not alter the levels of certain TCR Vβ. In a functional assay addressing cross-reactivity, Vβ binding superantigens were found to form one group, whereas SEH has different properties that fit well with Vα reactivity. As SEH binds on top of MHC class II, an interaction between MHC and TCR upon SEH binding is not likely. This concludes that the specific expansion of TCR Vα is not due to contacts between MHC and TCR, instead we suggest that SEH directly interacts with the TCR Vα domain.

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Section: Discussionmentioning

confidence: 63%

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Petersson

Pettersson

Skartved

et al. 2003

The Journal of Immunology

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“…The sequential assignment of the SEH protein was reported elsewhere 20 . According to the chemical shift index, the structural integrity of the SEH protein in solution shows no deviation from the reported crystal structures 16,20 . An NMR study of the transient interaction between SEH and the TCR was performed.…”

Section: Resultsmentioning

confidence: 77%

“…2a), with a total root mean square deviation (RMSD) of 1.2 Å calculated using secondary structure matching (SSM), where differences in the TCRβ chain contribute the most. Overall, the structural rearrangements upon complex formation are rather small; hence, the different proteins included in the complex are analogous with the uncomplexed structures [16][17][18] . SEH has an N-terminal OB-fold comprising of the β-strands β 1 -β 5 and one α-helix (α 3 ).…”

Section: Resultsmentioning

confidence: 99%

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

et al. 2010

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superantigens (sAgs) are bacterial toxins that interact with immunoreceptors, T cell receptor (TCR) and major histocompatibility complex (mHC) class II, conventionally through the variable β-domain of TCR (TCRVβ). They induce a massive release of cytokines, which can lead to diseases such as food poisoning and toxic shock syndrome. In this study, we report the X-ray structure of the ternary complex between staphylococcal enterotoxin H (sEH) and its human receptors, mHC class II and TCR. The structure demonstrates that sEH predominantly interacts with the variable α-domain of TCR (TCRVα), which is supported by nuclear magnetic resonance (nmR) analyses. Furthermore, there is no contact between mHC and TCR upon complex formation. structural analyses suggest that the major contact points to TCRVα are conserved among other bacterial sAgs. Consequently, a new dimension of sAg biology emerges, suggesting that in addition to the conventional interactions with the TCRVβ domain, sAgs can also activate T cells through the TCRVα domain.

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“…Third, zinc may indirectly participate in the interactions between SAgs and host receptors, by inducing conformational changes in certain SAgs; such changes could facilitate the binding of such SAgs to their receptors. Although direct evidence to support this hypothesis is lacking, comparisons of crystal structures of several SAgs with/without Zn 2+ indeed revealed that there are conformational changes associated with Zn 2+ binding (Baker et al, 2004a;Hakansson et al, 2000;Papageorgiou et al, 2004). In addition, although there is currently no evidence to support the following possibility, zinc could be required for interactions with co-stimulatory receptors for T-cell activation.…”

Section: Discussionmentioning

confidence: 99%

Mutagenesis, biochemical, and biophysical characterization of Mycoplasma arthritidis-derived mitogen

Li¹,

Zhao²,

Guo³

et al. 2007

Molecular Immunology

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Mycoplasma arthritidis -derived mitogen (MAM) is a superantigen (SAg) that can activate large fractions of T cells bearing particular TCR Vβ elements. Here we report the mutagenesis, biochemical and biophysical studies on the dimerization of MAM in solution. Our studies showed that although MAM mainly exists as a monomer in solution, a small percentage of MAM molecules form homodimer at high protein concentration, regardless of the presence of Zn 2+ . A distinct peak corresponding to a MAM homodimer was detected in the presence of EDTA, using both chemical cross-linking and analytical ultracentrifugation methods. Further mutagenesis studies revealed that single mutation of residues at the interface of the crystallographic dimer of MAM does not significantly affect the dimerization of MAM in solution. Circular dichroism (CD) analysis indicated that addition of Zn 2+ does not induce conformational changes of MAM from its apo-state. Thermal denaturation experiments indicated that addition of Zn 2+ to MAM solution resulted in a decrease of melting point (T m ), whereas addition of EDTA did not affect the T m of MAM. These results imply that there is no defined Zn 2+ -binding site on MAM.

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The crystal structure of staphylococcal enterotoxin H: implications for binding properties to MHC class II and TcR molecules

Cited by 49 publications

References 57 publications

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

Mutagenesis, biochemical, and biophysical characterization of Mycoplasma arthritidis-derived mitogen

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