The amino acid sequence of peptide S8, defined by residues 69 to 84 of the bovine myelin basic protein, was synthesized and shown to induce experimental allergic encephalomyelitis (EAE) in Lewis rats. Comparison of the sequence of peptide S8, H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH, to the corresponding region of the guinea pig myelin basic protein revealed the absence of Gly-His, residues 77 and 78, from the latter. Deletion of Gly-His from peptide S8 rendered the resulting peptide S49, a potent encephalitogen in Lewis rats.
Studies done with sequences shorter than synthetic peptide S49 revealed that the sequence of peptide S50, H-Ala-Gln-Arg-Pro-Gln-Asp-Glu-Asn-OH, made up of the C-terminal eight residues of peptide S49, was as encephalitogenic as the parent peptide. The sequence of peptide S50, not found naturally in any of the reported basic protein sequences, was generated by modification of the native bovine sequence of peptide S8. Unlike peptide S50, the sequence of peptide S53, H-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-OH, has a natural Gly-His deletion and is native to the sequence of guinea pig myelin basic protein. Despite Ser substitutions for Ala and Pro, peptide S53 is as encephalitogenic as peptide S50. The results of this study define an amino acid sequence from the guinea pig basic protein essential for inducing EAE in Lewis rats. Unlike previous studies, modification of a specific natural sequence generated a potent encephalitogenic determinant.
This work was supported by Grants No. 5 R01-NS-12316-03 from the National Institutes of Health, No. RG 1063-B-4 from the National Multiple Sclerosis Society and from the Margaret T. Biddle Foundation.