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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.

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BROSTOFF, S., LEVIT, S. & POWERS, J. Induction of experimental allergic neuritis with a peptide from myelin P2 basic protein. Nature 268, 752–753 (1977). https://doi.org/10.1038/268752a0

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