Experimental allergic encephalitis serves as a model for the study of therapies for demyelinating disease of the central nervous system. Its similarity to multiple sclerosis lies not only in clinical features and pathology, but more importantly like MS susceptibility to EAE is linked closely to immune response genes of the major histocompatibility complex (MHC). It has been shown that treatment in vivo with monoclonal antibody to the cell surface product of the susceptibility gene (I-A antiger can prevent the induction of acute EAE, and reverse the course of chronic EAE. Similar observations have been made with other autoimmune disease wherein susceptibility was linked to IR genes of the MHC. While the precise mechanism of action of anti I-A antibody is not known, it is quite clear from a number of systems that its actions are multimodal. This proposal attempts to characterize the haplotype specific nature of suppression of EAE using F1 restricted T cell lines and clones. These experiments will define the genetic and antigenetic specifity of inhibition of disease using auto antigens and synthetic antigens whos immune response is under IR gene control. At present, the mechanism by which IR genes confer susceptibility to disease is not known. Understanding mechanisms by which antibody to IR gene products regulate auto immune disease might lead to an improved knowledge of the pathogenesis of EAE.
