Defective T helper cell epitope responsible for the failure of region 69-84 of the human myelin basic protein to induce experimental allergic encephalomyelitis in the Lewis rat

Studies from our laboratory have shown that region 69-84 (synthetic peptide S49S) of myelin basic protein (MBP) defines an encephalitogenic sequence for experimental allergic encephalomyelitis (EAE) in Lewis rats. The most potent EAE inducers are the guinea pig MBP (Gp-MBP) and region 69-84, known as synthetic peptide Gp-S49S: (See text: formula). Human (H-MBP) was considerably less potent than Gp-MBP, and region 69-84 (H-S49S) of H-MBP did not induce hind leg paralysis or any histological signs of EAE. Since the development of EAE requires the expression of specific T and B cell epitopes, sequence analysis of H-S49S and Gp-S49S revealed phylogenetic variations in the H-S49S sequence, characterized by positions 77 and 78, and substitution of Ser with Thr at position 80: (See text: formula). Like Gp-S49S, peptide H-S49S induced the formation of antibodies with specificities directed against the C-terminal of the H-S49S, Gp-S49S, and homologous sequences. In contrast to Gp-S49S, neither II-S49S nor shorter peptides induced clonal T cell expansion when either of the peptides was added to encephalitogenic T cell clone D in culture. Clone D, which expresses T helper phenotype, was selected from encephalitogenic peptide-primed Lewis rats. The results of the study show that the failure of H-S49S to induce EAE is related to sequence alterations in the T helper cell epitope but not in the B cell epitope located in the N- and C-terminal portions of the S49S sequence, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)