Induction of experimental allergic neuritis with a peptide from myelin P₂ basic protein

Abstract

EXPERIMENTAL allergic neuritis (EAN) is an autoimmune demyelinating disease of the peripheral nervous system (PNS) produced in animals by injection of homogenates of PNS tissue¹ or PNS myelin² emulsified with Freund's complete adjuvant. Although it has been produced in such species as rabbits¹, guinea pigs³, and mice³, the neuritogenic determinant has not been identified. In experimental allergic encephalomyelitis (EAE), the central nervous system (CNS) counterpart of EAN, the encephalitogen is the myelin basic protein⁴. PNS myelin has two basic proteins, P₁ and P₂⁵, and the latter has been suggested to be the neuritogen². In attempts to induce the disease with intact P₂ (refs 6–9), mild symptoms of EAN were occasionally produced, but these were inconsistent. P₂ was implicated as the neuritogen when circulating lymphocytes of animals with EAN induced by injection of whole PNS myelin¹⁰ were found to be sensitised to P₂ but not P₁. Physicochemical studies of P₂ have demonstrated a very stable β structure in aqueous solution¹¹. Because the conformation is likely to differ in solution and in intact myelin, it is likely that the neuritogenic determinant(s) are altered. We have, therefore, tested peptides derived from the protein in order to minimise alteration of any neuritogenic determinant by extraneous port s of the intact molecule. We have identified a neuritogenic determinant within P₂—within a peptide representing the NH₂-terminal 21 amino acids of P₂.