T-CELL RECOGNITION OF AN IMMUNODOMINANT MYELIN BASIC-PROTEIN EPITOPE IN MULTIPLE-SCLEROSIS

MULTIPLE sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen1,2. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis3,4 and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein5. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQwl (refs 6-9). To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRwll phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQwl-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals. © 1990 Nature Publishing Group.