Specific Immunotherapeutic Strategies: Lessons from Myelin Basic Protein-Induced Experimental Allergic Encephalomyelitis

The progress of research on the pathogenesis and treatment of multiple sclerosis (MS), the principal human demyelinating disease of the central nervous system (CNS) , has intensified in the past 3 years. In part, this is due to the application of advances in molecular biology, like polymerase chain reaction (PCR), and to developments in cellular immunology, like technology for the growth of T-cell clones. Many lessons that have been learned in an animal model of CNS demyelinating disease, experimental allergic encephalomyelitis (EAE), have been verified in the human disease MS. Indeed, certain successful approaches for treatment of EAE are being attempted in MS at the present time. This review describes the strong parallels that exist between T-cell receptor (TCR) usage in the pathogenesis of EAE, TCR usage in myelin basic protein (MBP)-specific T-cells in the peripheral blood of MS patients (Wucherpfennig et al. 1990; Ota et al. 1990; Martin et al. 1991) and in T-cells in demyelinative plaques in MS brain (Oksenberg et al. 1990). Based on these similarities, selective immunotherapy that targets either class II molecules of the major histocompatibility complex (MHC) or TCR variable regions will be described in EAE, with consideration given to application of these principles in MS. These new therapeutic approaches involve monoclonal antibodies (mAbs) directed to either HLA class II molecules or TCR V region molecules, or peptides that compete with HLA class II molecules or vaccinate against TCR V regions.