Pathway to destruction: How “superantigens” attack

What do flesh-eating disease, food poisoning and toxic shock syndrome have in common?

These rapid-onset diseases are all caused by tiny amounts of bacterial “superantigens”, which are toxins secreted by some bacteria that trigger a massive activation of immune cells throughout the body. This systemic immune response then sets off its own chain of damaging biochemical events that can lead not only to fever and vomiting but multiple organ failure and death.A new study from Robarts Research Institute-published today in the journal Immunity describes for the first time the precise molecular chain of events that initiates this wide-scale immune response, moving us a step closer to the development of targeted drug therapies for these devastating diseases.Superantigens are also of interest in two other areas: as potential triggers of autoimmune diseases, such as rheumatoid arthritis, and as possible agents of biological warfare. Staphyloccocus enterotoxin B, for example, can be spread by inhalation, can be 100 per cent lethal and has no known antidote.While scientists understand how many other invaders activate T cells to mount an immune response-through a cascade of biochemical signals that begin with them binding to particular receptors and co-receptors on the surface of cells-what has not been clear is how bacterial superantigens can also activate these cells in the absence of an important known co-receptor.”Our work identifies an alternate molecular pathway within the T cell that is triggered by these superantigens and goes on to produce this massive, damaging immune attack,” explained Robarts scientist Dr. Joaquin Madrenas, who holds a Canada Research Chair in Transplantation and Immunobiology. He is also Director of London’s FOCIS Centre for Clinical Immunology and Immunotherapeutics and is a Professor of Microbiology and Immunology at The University of Western Ontario. Dr. Madrenas led the study with collaborators in London, Ont., and San Diego.”The triggering of this pathway suggests that these toxins use a certain super-family of receptors (G protein-coupled receptors) to signal to the cell,” Dr. Madrenas added. “The next step is to identify which receptor in that family is involved-that will then offer a target for an antidote.” (Source: Immunology: Robarts Research Institute: July 2006).