Neural antigens and the development of autoimmunity

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune demyelinating disease of the CNS. The disease, EAE, is similar to acute multiple sclerosis in man. Induction and regulation of EAE is governed by immune responses to specific regions of the myelin basic protein (MBP). These regions are species specific with defined sequence boundaries that are not subject to modification without loss of activity. The region which induces EAE in guinea pigs is defined by a nine-residue sequence and, like the parent MBP, activates a T lymphocyte subset responsible for demyelination. Substitution and/or deletion of specific amino acids from the nine-residue sequence destroys its ability to induce disease and gives rise to a sequence, normally subsumed within the disease-inducing one, capable of activating T suppressor cell function responsible for EAE-regulation. Thus, the development of EAE is contingent upon recognition of the complete, but not a portion of the disease-inducing determinant of the MBP. Recognition of a portion of the determinant generates a particular type of delayed type hypersensitivity incapable of inducing disease but capable of regulating disease development.