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

G. A. Hashim, A. B. Galang, J. V. Srinivasan, E. F. Carvalho, H. Offner, A. A. Vandenbark, W. L. Cleveland, E. D. Day

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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: (Formula Presented.) 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 deletion of Gln (No.76), insertion of His‐Gly at positions 77 and 78, and substitution of Ser with Thr at position 80: (Formula Presented.) 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 H‐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. Also, the results suggest that the EAE activity of H‐MBP may be related to either a second EAE region that expresses T helper and B cell functions or to a dislocated T helper cell epitope that operates in conjunction with the B cell epitope located in the C‐terminal region of the H‐S49S sequence.

Original languageEnglish (US)
Pages (from-to)222-230
Number of pages9
JournalJournal of Neuroscience Research
Volume24
Issue number2
DOIs
StatePublished - Oct 1989

Keywords

  • B cell epitopes
  • MBP
  • T cell epitope
  • peptides

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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