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. 2011 Sep;9(9):e1001145.
doi: 10.1371/journal.pbio.1001145. Epub 2011 Sep 13.

Clarifying the mechanism of superantigen toxicity

John D Fraser  1
Affiliations

Clarifying the mechanism of superantigen toxicity

John D Fraser. PLoS Biol. 2011 Sep.
No abstract available

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Conflict of interest statement

The author has declared that no competing interests exist.

Figures

Figure 1
Figure 1. The model structures of four trimer complexes reveal the diversity in Sags binding.
In the first structure, SEC3 (similar to SEB) is bound to the conserved MHC class II α-chain and engages a Vβ8 domain ,. Note how the TcR makes no contact with the normal peptide/MHC surface as it would during normal peptide recognition. In the second structure TSST binds in the same location as SEC3 but in a different orientation. TSST is very specific for the human Vβ2 TcR ,. In the third structure, the streptococcal Sag SPEC is bound to the other side of MHC class II and ligates human Vβ2 TcR , but in a quite different orientation to TSST. The fourth structure is of staphylococcal enterotoxin H (SEH) bound to the β-chain of MHC class II but ligating a TcR through its Vα27 domain—the only Sag known to engage a TcR α-chain . In each of the structures the location of the CD28 binding identified by Arad et al. is represented by red space filling spheres. Note its position well away from both TcR and MHC class II in a suitable position to engage a CD28 molecule in a tetrameric membrane complex in each of the four Sag orientations.
Figure 2
Figure 2. A cartoon of what might be happening at the immunological synapse during Sag engagement.
In a model consistent with the crystal complexes shown in Figure 1, CD28 provides the essential 2nd co-stimulatory signal through separate B7 ligation. CD28 is essential for Sag toxicity ,. In the new model proposed on the right, CD28 is part of a larger more stable complex directly ligated by Sag. This new model explains much better the extreme potency and cytokine toxicity observed with Sags. In theory this tetrameric complex would be more stable being held together by 3 interactions rather than 2.
See this image and copyright information in PMC

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