Molecular Bases for the Difference in the Potency of Myelin Basic Protein from Different Species in Lewis Rats

  • George A. Hashim
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 100)


The results of this study define the chemical bases for the difference in the encephalitogenic potency reported for the bovine and guinea pig myelin basic proteins. Studies with synthetic peptides showed that the sequence of peptide S53, H-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-OH, which is native to the guinea pig basic protein, is the minimum amino acid sequence necessary for inducing EAE in Lewis rats. The results of this study further showed that specific sequence modifications rendered the native bovine sequence highly encephalitogenic.


Synthetic Peptide Myelin Basic Protein Basic Protein Experimental Allergic Encephalomyelitis Citraconic Anhydride 
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  1. 1.
    Alvord, E.C. Jr., Etiology and pathogenesis of experimental allergic encephalomyelitis, in The Central Nervous System ( 0.T. Bailey and D.E. Smith, eds.), The Williams and Wilkins Co., Baltimore (1968) pp. 52–70.Google Scholar
  2. 2.
    Alvord, E.C. Jr., Acute disseminated encephalomyelitis and allergic neuroencephalopathies, in Handbook of Clinical Neurology Vol. 9 ( P.J. Vinken and G.W. Bruyn, eds.) North-Holland Publishing Co., Amsterdam (1970) pp. 500–571.Google Scholar
  3. 3.
    Brostoff, S.W. and Eylar, E.H., The proposed amino acid sequence of the P1 protein of rabbit sciatic nerve myelin, Arch. Biochem. Biophys. 153 (1972) 590–598.Google Scholar
  4. 4.
    Carnegie, P., Properties, structure and possible neuroreceptor role of the encephalitogenic protein of human brain, Nature 229 (1971) 25–28.PubMedCrossRefGoogle Scholar
  5. 5.
    Caspary, E.A. and Field, E.J., An encephalitogenic protein of human origin: some chemical and biological properties, Ann. N. Y. Acad. Sci. 122 (1965) 182–198.PubMedCrossRefGoogle Scholar
  6. 6.
    Chou, J. C-H., Chou, F. C-H., Kowalski, T.J., Shapira, R. and Kibler, R.F., The major site of guinea pig myelin basic protein encephalitogenic in Lewis rats, J. Neurochem. 28 (1977) 115–119.PubMedCrossRefGoogle Scholar
  7. 7.
    Dunkley, P.R., Coates, A.S. and Carnegie, P., Encephalitogenic activity of peptides from the smaller basic protein of rat myelin, J. Immunol. 110 (1973) 1699–1701.PubMedGoogle Scholar
  8. 8.
    Einstein, E.R., Chao, L.P., Csejtey, J., Kibler, R. and Shapira, R., Species specificity in response to tryptophan modified encephalitogen, Immunochemisyr 9 (1972) 73–84.CrossRefGoogle Scholar
  9. 9.
    Eylar, E.H., Brostoff, S., Hashim, G.A., Caccam, J. and Burnett, P., Basic Al protein of the myelin membrane. The complete amino acid sequence, J. Biol. Chem. 246 (1971) 5770–5784.PubMedGoogle Scholar
  10. 10.
    Eylar, E.H. and Hashim, G.A., Allergic encephalomyelitis: cleavage of the C-tryptophyl bond in the encephalitogenic basic protein from bovine myelin, Arch. Biochem. Biophys. 131 (1969) 215–222.CrossRefGoogle Scholar
  11. 11.
    Eylar, E.H., Salk, J., Beveridge, G.C. and Brown, L.V., Experimental allergic encephalomyelitis: an encephalitogenic basic protein from bovine myelin, Arch. Biochem. Biophys. (1969)132: 34–48.Google Scholar
  12. 12.
    Hashim, G.A., Experimental allergic encephalomyelitis in Lewis rats: chemical synthesis of disease-inducing determinant, Science 196 (1977) 1219–1221.PubMedCrossRefGoogle Scholar
  13. 13.
    Hashim, G.A., Carvalho, E.F. and Sharpe, R.D., Definition and synthesis of the essential amino acid sequence for experimental allergic encephalomyelitis in Lewis rats, J. Biol. Chem. (1977), submitted for publication.Google Scholar
  14. 14.
    Hashim, G.A. and Eylar, E.H., Allergic encephalomyelitis: isolation and characterization of encephalitogenic peptides from the basic protein of bovine spinal cord, Arch. Biochem. Biophys. 129 (1969) 645–654.CrossRefGoogle Scholar
  15. 15.
    Hashim, G.A. and Schilling, F.J., Prevention of experimental allergic encephalomyelitis by nonencephalitogenic basic peptides, Arch. Biochem. Biophys. 156 (1973) 287–297.CrossRefGoogle Scholar
  16. 16.
    Hashim, G.A. and Sharpe, R.D., Experimental allergic encephalo- myelitis:the structural specificity of determinants for de- layed hypersensitivity, Immunochemistry 11 (1 974) 633–640.Google Scholar
  17. 17.
    Hashim, G.A. and Sharpe, R.D., Non-encephalitogenic synthetic analogues of the determinant for allergic encephalomyelitis in guinea pigs, Nature 255 (1975) 484–485.PubMedCrossRefGoogle Scholar
  18. 18.
    Hashim, G.A., Sharpe, R.D., Carvalho, E.F. and Stevens, L.E., Suppression and reversal of experimental allergic encephalomyelitis in guinea pigs with a non-encephalitogenic analogue of the tryptophan region of the myelin basic protein, J. Immunol. 116 (1976) 126–130.PubMedGoogle Scholar
  19. 19.
    Kies, M.W. and Alvord, E.C. Jr (eds.), Encephalitogenic activity in guinea pigs of water soluble protein fractions of nervous tissue, in Allergic Encephalomyelitis, Charles C. Thomas Co., Springfield, Ill. (1959) pp. 293–299.Google Scholar
  20. 20.
    McFarlin, D.E., Blank, S.S., Kibler, R.F., McKneally, S. and Shapira, R., Experimental allergic encephalomyelitis in the rat: response to encephalitogenic proteins and peptides, Science 179 (1973) 478–480.PubMedCrossRefGoogle Scholar
  21. 21.
    Martenson, R.E., Deibler, G.E., Kies, M.W. and Levine, S., Myelin basic protein of mammalian and submammalian vertebrates: encephalitogenic activities in guinea pigs and rats, J. Immunol. 109 (1972) 262–270.PubMedGoogle Scholar
  22. 22.
    Martenson, R.E., Deibler, G.E., Kramer, A.J. and Levine, S., Comparative studies of guinea pig and bovine myelin basic proteins. Partial characterization of chemically derived fragments and their encephalitogenic activities in Lewis rats, J. Neurochem. 24 (1975) 173–182.PubMedCrossRefGoogle Scholar
  23. 23.
    Martenson, R.E., Levine, S. and Sowinski, R., The location of regions in guinea pig and bovine myelin basic proteins which induce experimental allergic encephalomyelitis in Lewis rats, J. Immunol. 114 (1975) 592–596.Google Scholar
  24. 24.
    Merrifield, R.B., Solidphase peptide synthesis. III. An improved synthesis of bradykinin, Biochemistry 3 (1964) 1385–1390.Google Scholar
  25. 25.
    Nakao, A., Davis, W.J. and Einstein, E.R., Basic protein from the acidic extract of bovine spinal cord. I. Isolation and characterization, Biochim. Biophys. Acta 130 (1966) 163–170.CrossRefGoogle Scholar
  26. 26.
    Shapira, R., McKneally, S., Chou, F. C-H., and Kibler, R.F., Encephalitogenic fragment for myelin basic protein. Amino acid sequence of bovine, rabbit, guinea pig, monkey and human fragments, J. Biol. Chem. 246 (1971) 4630–4640.Google Scholar
  27. 27.
    Swanborg, R.H., Immunological response to altered encephalitogenic protein in guinea pigas, J. Immunol. 102 (1969) 381388.Google Scholar
  28. 28.
    Swanborg, R.H. and Amesse, L.S., Experimental allergic encephalomyelitis: species variability of the encephalitogenic determinant,J. Immunol. 107 (1971) 281–283.PubMedGoogle Scholar
  29. 29.
    Waksman, B.H., Experimental allergic encephalomyelitis and the “auto-allergic” diseases, Int. Arch. Allergy Suppl. 14 (1959) 1–87.Google Scholar
  30. 30.
    Westall, F.C., Robinson, A.R., Caccam, J., Jackson, J. and Eylar, E.H., Essential chemical requirements for induction of allergic encephalomyelitis, Nature 229 (1971) 22–24.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • George A. Hashim
    • 1
  1. 1.Department of Surgery and MicrobiologySt. Luke’s Hospital Center, and Columbia UniversityNew YorkUSA

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