[Effect of superantigens on the development of neuroimmunological disorders]

Superantigens (SA) bind to major histocompatibility complex (MHC) class II antigens and activate T cells through a specific interaction between the V beta region of the T cell receptor and the toxin. Therefore, it has been postulated that SA may trigger or modulate the development of autoimmune diseases caused by T cells. In this report, the effects of SA on the development of experimental and human neurological autoimmune diseases are reviewed and the possibility of the involvement of retroviral SA in the development of human diseases is discussed. In experimental autoimmune encephalomyelitis (EAE), administration of SA prior to antigen challenge protects animals from EAE, whereas the same treatment after antigen challenge augments EAE development. These findings suggest either that 1) exposure of individuals to bacterial toxins during infection stimulates a few potentially autoreactive T cells that have escaped from the process of tolerance to expand above a threshold level, permitting autoattack, or that 2) the toxin suppresses autoreactive T cells which have the capability of inducing autoimmune diseases. In human neuroimmunological diseases such as multiple sclerosis, circumstantial evidence suggests that retroviral SA might be associated with disease development, but no direct proof has been presented so far. The possible reasons for this are also discussed.