Superantigens

• Superantigens are toxins produced by commonly encountered staphylococcal and streptococcal bacteria.
• More than 40 divergent superantigens have been recognized to date.
• Superantigen toxins elicit a vastly exaggerated immune response, up to 50,000 times more potent than the response induced by ordinary antigens, resulting in a Th1 cytokine ‘storm’ that leads to toxic or septic shock.
• Death or incapacitation by natural mixtures of superantigen toxins constitutes an as yet unsolved medical problem as well as a bioterror threat; there is no available therapeutic nor a vaccine.
• Superantigens bypass the restricted presentation of conventional antigens, binding directly to the MHC class II molecule, the T cell receptor and a novel third receptor discovered by Atox Bio's scientists.
• The subversion of the third host receptor, for use as a receptor by superantigens, may be employed more widely by pathogens.

Clinical utility of superantigen antagonists

• Superantigen antagonist for treatment of acute diseases:
• Toxic shock - Resulting from sudden and massive induction of Th1 cytokines (interleukin-2, interferon- and tumor necrosis factor) produced by superantigen-stimulated immune cells.
• Gram-positive septic shock – Also involving an acute effect of superantigens on the immune system.
• Use of superantigen antagonists as immunomodulators for treatment of chronic / long-term diseases:
• Autoimmune diseases – By modulating the nature of the immune response and blocking an exaggerated Th1 response even in the absence of superantigens, these antagonists act as immunomodulators. As such, they are potentially useful for the treatment of autoimmune diseases caused by chronic overproduction of Th1 cytokines, for example in multiple sclerosis, rheumatoid arthritis and psoriasis.