Evidence is emerging that the major T- and B-cell response in multiple sclerosis (MS) is directed to a region of myelin basic protein (MBP) between residues 84 and 103. In rodent models of MS, immunization to this component of MBP evokes experimental autoimmune encephalomyelitis (EAE). T cells found in EAE lesions show similarities in the VJ and VDJ regions of their alpha and beta chains with T cells in MS lesions, and with T cells that are specific for MBPp84-103 isolated from patients with MS. If this region of MBP is critical in the pathogenesis of MS, then therapy aimed at controlling the immune response to this immunodominant region of MBP may be beneficial in treating MS.