[Superantigens and autoimmune diseases]

Superantigens are potent immunomodulators derived from microorganisms such as bacteria, viruses and mycoplasmas. Their effects on immune systems are obtained through their binding both to outer portion of binding grooves of an MHC on antigen presenting cells and to non-recognizing structure of hypervariable region of T cell antigen receptors. X-ray crystallography revealed precise structures of some superantigens, a beta barrel domain as a ligand to MHC class II alpha chain and a beta grasp domain to TCRV beta chain. Superantigens induce not only T/B cell activation but also immunological tolerance through oligoclonal deletion and/or anergy. Contribution of superantigens to the pathogenesis of autoimmune diseases has been discussed since a superantigen, mycoplasma arthritis T cell mitogen revealed to be arthritogenic to mice, and the murine arthritis resembled human rheumatoid arthritis in the pathological findings. Rheumatoid arthritis as well as Kawasaki Disease, Sjögren syndrome, and multiple sclerosis is now well studied through the oligoclonal expression of TCR beta specificities on infiltrating T cells. Application of superantigens to the treatment of autoimmune diseases is also discussed.