Incidence of Histological and Clinical Signs of EAE in Lewis , BN , (

Experimental allergic encephalomyelitis (EAE) 1 has been widely studied as a possible experimental model for human demyelinative diseases, the two most common of which are multiple sclerosis and acute disseminated encephalomyelitis. EAE is also the only experimental autoimmune disease for which the exact amino acid sequence of an inciting molecule, basic protein of myelin, is known (1). Nearly identical basic proteins are found in all mammalian myelin studied and an encephalitogenic nonapeptide fragment of the bovine basic protein, which has been both isolated and synthesized de novo, has been shown to be encephalitogenic on a molar basis at least equivalent to the 170 amino acid basic protein (2). Thus, EAE also provides an attractive model for studying the immunological mechanisms of autoimmune diseases in general. In view of the rapidly accumulating evidence of genetic control of immune responses by genes linked to the major histocompatibility locus of the species (3), it is now appropriate to determine whether autoimmunity might also be influenced by specific histocompatibility-linked immune response genes. Two independent groups have observed a significant correlation between certain HL-A specificities and presence of multiple sclerosis (4) .~ Susceptibility to experimental autoimmune rnurine thyroiditis was recently shown to be genetically linked to the H-2 locus (5). Since EAE is both a possible model for multiple sclerosis and a prototype experimental autoimmune disease in several species, we are currently studying its genetic control. Data presented here show that susceptibility to the induction of histologically determined EAE by injection of purified guinea pig basic protein is determined by a gene, designated Ir-EAE, linked to the major histocompatibility locus in the rat.