Peptides and autoimmune disease

Abstract

The use of derived and synthetic peptides has contributed greatly to our understanding of encephalitogenic determinants in the basic protein molecule. Peptides derived from BP by use of trypsin, pepsin, cathepsin D (brain and liver) and BNPS-skatole have proven most useful. Synthetic peptides have served to define the disease-inducing determinants with precision. A remarkable feature of these studies is that different antigenic determinants serve as encephalitogenic sites in different species. The encephalitogenic sites comprise short peptide domains of the BP polypeptide chain, only 8 residues (rat), 9 residues (guinea pig), and 10 residues (rabbit) in length. In view of the requirement for both haptenic and carrier specificity of an immunogenic molecule, it is impressive that these peptides themselves elicit the autoimmune disease, EAE. While less active than BP on a molar basis, they are nonetheless potent encephalitogens, producing clinical signs in rats and guinea pigs at less than 1 microgram dose. The data indicate that for most animal species (guinea pig, rat, monkey) there appears to be only one major encephalitogenic determinant, an unusual finding in view of the number of antigenic determinants for cell-mediated immunity existing in the BP molecule. Possibly a combination of genetic and anatomical factors may account for this phenomenon. A relationship may exist between multiple sclerosis and EAE as shown by peptide studies; lymphocytes are found in MS patients during exacerbation sensitized to the same region of BP active in the monkey. The major encephalitogenic sites are: Guinea Pig (9) Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys(Arg); Rabbit (10) Thr-Thr-His-Tyr-Gly-Ser-Leu-Pro-Gln-Lys; Rat (8) Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn; Monkey (14) Phe-Lys-Leu-Gly-Gly-Arg-Asp-Ser-Arg-Ser-Gly-Ser-Pro-Hser.