AbstractThe presence of a sequestered encephalitogenic determinant for Lewis rats in the bovine myelin BP was demonstrated with synthetic peptide sequences prepared in our laboratory by the Merrifield solidphase method. The sequence of the encephalitogenic determinant (residues 75‐84) from bovine BP (peptide S6), H‐Ala‐Gln‐Gly‐His‐Arg‐Pro‐Gln‐Asp‐Glu‐Asn‐OH, is similar but not identical to the sequence reported for the guinea pig BP (peptide S53), H‐Ser‐Gln‐(–)‐(–)‐Arg‐Ser‐Gln‐Asp‐Glu‐Asn‐OH. The presence or the absence of Gly‐His from the sequence of either the bovine or the guinea‐pig determinants did not alter their encephalitogenic potencies; however, the presence of Gly‐His at positions 77 and 78 together with H‐Gly‐Ser‐Leu‐Pro‐Gln‐Lys‐ (residues 69‐74) at the N‐terminal end of the bovine determinant destroyed its encephalitogenic potency.In contrast to the absence of Gly‐His from the potent encephalitogenic guinea‐pig BP, guinea‐pig fragment 44‐89, and synthetic peptide S49, its presence in the bovine sequence prevents recognition of this determinant and renders the parent bovine BP, bovine fragment 44‐89, and synthetic peptide S8 (residues 69‐84) relatively non‐encephalitogenic. The results of this study suggest that intramolecular interactions occur between adjacent amino acids, conferring secondary or tertiary structures upon this region of the bovine BP which renders the encephalitogenic determinant inaccessible for recognition by the host animal. The presence of sequestered disease‐ind