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Presented by: Shymaa Yousry Hassan [602]

Superantigens are medium sized 22-29 kDa

globular compact proteins. Crystal structures: ellipsoidal proteins with characteristic two domain protein folding. Have sites for binding MHC II and TCRs.

Two-domain folding pattern and architecture
(N and C terminal domains and helix in the center of the molecule)

NH2-terminal barrel globular domain known as

the oligosaccharide/oligonucleotide fold Long -helix that diagonally spans the center of the molecule COOH terminal globular domain

The N terminal domain:
Hydrophobic residues in solvent exposed regions Determines the lethality of the toxin.

The C terminal domain:

Four stranded sheet capped by the central helix
Determines the superantigenicity of the toxin.

Each superantigen possesses slightly different

binding modes when it interacts with MHC class II molecules or the T-cell receptor.

Special characters
Presence of disulphide loop formed by the

cystinyl residues (except in TSST I) in the N terminal domain [emetic properties of the enterotoxins]. TSST-I: no extrastructural characters=> cleaved by

SE and SPE: extrastructural characters like: Lengthy amino terminal [resist the peptide digestion in the stomach => Staphylococcal food poisoning]. Emetic property: cystinyl residues.


The unique feature of superantigen is that it

bypasses the antigen processing mechanism and specifically binds to TCR v segment and forms a trimolecular complex along with major histocompatibility complex class II.

Mechanism of action.
Superantigens bind to MHC class II molecules of

antigen presenting cells and V region of T-cell receptor in a non-antigen-specific manner. Stimulation of large number of T cells resulting in cell activation, differentiation, proliferation, and production of cytokines involved in various inflammatory processes.


Effects of superantigen stimulation

IL - I and TNF- bring about the vascular

endothelial injury [toxic shock syndrome]. of IL- 6, GM-CSF and E-selectin elicit proinflammatory and prothrombic responses [Kawasaki syndrome].

Direct Effects
Th cells: IL-1, IL-2, IL-6, TNF-, Macrophage

Inflammatory protein, Macrophage chemoattractant protein. Fever, rash, multi organ failure, coma & death. IL-10 [non responsive memory cells]: Deletion of activated T. INF : prolonged SAg exposure, induces auto immunity[Kawasaki disease] MHC cross-linking: up-regulates apoptosis.

Indirect Effects
Mitogenic activity.
Monocytic cell activation & release of large

amounts of TNF-: tissue necrosis Induce gastrointestinal toxicity and cause emesis: by SAg produced by bacteria causing food poisoning [SE and SPE].

Interaction of T cell receptor (TCR) and MHC loaded with antigenic

peptide during the normal T cell activation (A) and during superantigenic activation by staphylococcal enterotoxins (B). The latter can be inhibited by polyclonal antibodies such as anti-SEB hyperimmune serum as shown in (C).

Indirect Effects
Monocytic cell activation and release of large

amounts of TNF- leading to tissue necrosis. Emesis: by SAg produced by bacteria causing food poisoning. Induction of gastrointestinal toxicity and emesis.

Shock: massive release of cytokines.
Immunosupression: uncoordinated activation of

immune system. Autoimmunity: bypass of auto reactive T & B cells