T and B cell responses to myelin basic protein and encephalitogenic epitopes.

The major encephalitogenic epitope of myelin basic protein (MBP) for the Lewis rat includes residues 68-84, although a minor epitope has been localized to MBP residues 87-99. We synthesized MBP68-84 and MBP87-99, and immunized rats with these peptides or with MBP in complete Freund's adjuvant (CFA). MBP and MBP68-84 induced paralytic experimental autoimmune encephalomyelitis (EAE) at equimolar concentrations, whereas significantly higher dosages of MBP87-99 were required to elicit paralytic disease. Spleen cells (SpC) from MBP- or MBP68-84-immunized rats could be activated with either MBP or MBP68-84 to transfer EAE to recipients. Anti-MBP antibodies were detected by ELISA in rats immunized with MBP-CFA, and anti-MBP68-84 specific antibodies were present in serum obtained from MBP68-84-immunized animals. However, these antibodies were non-cross reactive. MBP87-99 elicited only a meager antibody response to the immunizing peptide, and cross reactivity with MBP was not observed. Thus, although MBP and each peptide exhibited encephalitogenic activity, and MBP and MBP68-84 were cross reactive at the T cell level, the absence of cross reactivity at the humoral level indicates that significant immunological differences exist between MBP and the synthetic determinants, which may reflect differences in epitope recognition by T and B lymphocytes.