Chapter 7 : Structural Evidence for Zinc and Peptide Dependence in Superantigen-Major Histocompatibility Complex Class II Interaction

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Structural Evidence for Zinc and Peptide Dependence in Superantigen-Major Histocompatibility Complex Class II Interaction, Page 1 of 2

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Bacterial superantigens (SAgs) are small, highly mitogenic proteins that cross-link antigen-presenting cells (APCs) and T cells by binding simultaneously to the immunoreceptors major histocompatibility complex (MHC) class II and the T-cell receptors (TCRs) leading to the stimulation of large numbers of T cells. The advantages for microbes of secreting SAgs are not very well understood, but apart from disturbing the normal immune response they might prolong survival by promoting local inflammation, thereby increasing the blood and nutrient supply. The ability of SAgs to activate the immune system systemically became clear when evidence was presented that the interaction took place outside the antigen groove. SEA is an interesting SAg because it can interact with both the generic site on the α-chain of MHC class II and the zinc-dependent site on the β-chain of major histocompatibility complex (MHC) class II. The crystal structure shows that SED forms homodimers where two carboxy-terminal β-sheets from two SED molecules are packed against each other burying a large solvent-inaccessible area. At high concentrations the streptococcal SAg pyrogenic exotoxins (SPE-C) has the ability to cross-link two MHC molecules through a high-affinity, zinc-dependent interaction with the β-chain due to homodimer formation using residues in its amino-terminal domain (SPE-C probably binds MHC as a monomer under physiological conditions). Approximately two-thirds of the buried surface area is contributed by interaction with the β1-helix on MHC and one-third by the antigenic peptide, strongly implying that the peptide plays an important role in binding the SAg.

Citation: Walse B. 2007. Structural Evidence for Zinc and Peptide Dependence in Superantigen-Major Histocompatibility Complex Class II Interaction, p 103-120. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch7

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MHC Class II
Tumor Necrosis Factor alpha
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Image of Figure 1.
Figure 1.

Sequence alignment of a subset of SAgs. The alignment was created as a structural alignment by superpositioning different SAg structures. Secondary structural elements for SEA are indicated below the sequences. Residues involved in the zinc-dependent high-affinity interaction with the β-chain of MHC class II are indicated with black boxes and residues involved in the low-affinity interaction with the α-chain of MHC class II are indicated with gray boxes. The HExxH motif in SEC2, SEC3, and SPE-A is outlined with black lines.

Citation: Walse B. 2007. Structural Evidence for Zinc and Peptide Dependence in Superantigen-Major Histocompatibility Complex Class II Interaction, p 103-120. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch7
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Image of Figure 2.
Figure 2.

Family tree of streptococcal and staphylococcal SAgs. The tree was created using ClustalW ( ).

Citation: Walse B. 2007. Structural Evidence for Zinc and Peptide Dependence in Superantigen-Major Histocompatibility Complex Class II Interaction, p 103-120. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch7
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Table 1.

Crystal structures of bacterial SAgs and their complexes

Citation: Walse B. 2007. Structural Evidence for Zinc and Peptide Dependence in Superantigen-Major Histocompatibility Complex Class II Interaction, p 103-120. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch7

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