Suppression of the Immune Response: Reversal of the Disease State with Antigen in Allergic Encephalomyelitis

Abstract

EXPERIMENTAL allergic encephalomyelitis (EAE) is an autoimmune disease which is characterized^1,2 primarily by lymphocytic inflammation and demyelination of the white matter of the central nervous system (CNS); clinical signs generally include lower limb paralysis, ataxia, tremors and death^3,4. Of numerous factors proposed for EAE induction, it is now established that the A1 protein, the basic protein of CNS myelin (molecular weight 18,400), which comprises 30% of the myelin protein¹, is the encephalitogenic agent of CNS tissue^1,5,6. The complete amino-acid sequence of the bovine⁷ and human^7,8 A1 proteins has now been determined, thus making possible the correlation between chemical structure and immunological properties. The suggested open double-chain conformation⁹ of this protein, in contrast to a globular structure, emphasizes the primary structure in defining its antigenic properties, and has simplified the identification of the disease-inducing sites as they can be obtained as isolated peptide fragments. One peptide of forty-five amino-acids, residues 44–89 of the A1 sequence^10,11, induces EAE in the rabbit. A major encephalitogenic determinant¹² in both guinea-pigs and rabbits contains only nine amino-acids (residues 114–122) (refs. 13, 14) including the single tryptophan residue. Phylogenetic variation is emphasized by the finding¹⁵ of another region, residues 134–170, which defines the major encephalitogenic determinant for the rhesus monkey.