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Molecular mimicry and the autoimmune response to the peripheral nerve myelin PO glycoprotein

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Abstract

In the Lewis rat immunisation with the myelin PO glycoprotein can induce an inflammatory demyelinating disease of the peripheral nervous system, experimental allergic neuritis (EAN), which has many clinical and histopathological parallels with the human disease the Guillain-Barre syndrome. In view of the reported association of GBS with a number of infectious agents we have investigated whether “molecular mimicry” may occur between microbial antigens and the PO protein that could possibly trigger a similar pathogenic autoimmune response in man. A computer search of the available protein sequence data bases identified several absolute sequence homologies between PO and viral proteins that involve five or more consecutive amino acid residues. Four of these sequence homologies involved viral pathogens previously associated with the Guillain-Barre syndrome, namely Epstein-Barr virus (EBV), cytomegalovirus (CMV), Varicella zoster virus (VZV) and human immunodeficiency virus I (HIV I). Although, sequence homologies were also found between viral peptides and the neuritogenic determinants of PO, residues 56–71 and 180–199, these homologies proved incapable of eliciting EAN in the Lewis rat. These observations are discussed with reference to the role that molecular mimicry between T cell epitopes on pathogen derived antigens and the PO protein may play in the pathogenesis of the Guillain-Barre syndrome.

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Abbreviations

EAN:

Experimental allergic neuritis

EAE:

experimental allergic encephalomyelitis

PNS:

peripheral nervous system

CNS:

central nervous system

MBP:

myelin basic protein

GBS:

Guillain Barre syndrome

CFA:

complete Freund's Adjuvant

LPC:

lysophosphatidyl choline

VZV:

Varicella zoster virus

CMV:

cytomegalovirus

EBV:

Epstein Barr virus

HIV I:

human immunodeficiency virus I

References

  1. Waksman, B. H., and Adams, R. D. 1955. Allergic neuritis: an experimental disease of rabbits induced by injection of peripheral nervous tissue and adjuvants. J. Exp. Med. 102:213–234.

    Google Scholar 

  2. Linington, C., Wekerle, H., and Meyermann, R. 1986. T lymphocyte autoimmunity in peripheral nervous system disease. Agents and Actions 19:256–265.

    Google Scholar 

  3. Waksman, B. H., and Adams, R. D. 1956. A comparative study of experimental allergic neuritis in the rabbit, guinea pig and mouse. J. Neuropath. Exp. Neurol. 15:293.

    Google Scholar 

  4. Lampert, P. W. 1969. Mechanisms of demyelination in experimental allergic neuritis.-Electron microscopic studies. Lab. Invest. 20:127–138.

    Google Scholar 

  5. Kadlubowski, M., Hughes, R. A. C., and Gregson, N. A. 1980. Experimental allergic neuritis in the Lewis rat: characterization of the activity of the peripheral myelin and its major basic protein P2. Brain Rs. 184:439–454.

    Google Scholar 

  6. Izumo, S., C. Linington, Wekerly, H., and Meyermann, R. 1985. A morphological study on experimental allergic neuritis mediated by a T cell line specific for bovine P2 protein in the Lewis rat. Lab. Invest. 53:209–218.

    Google Scholar 

  7. Rostami, A-M., Burns, J. B., and Brown, M. J. 1985. Transfer of experimental allergic neuritis with P2-reactive T-cell lines. Cell. Immunol. 91:354–361.

    Google Scholar 

  8. Linington, C., Izumo, S., Suzuki, M., Uyemura, K., Meyermann, R., and Wekerle, H. 1984. A permanent rat T cell line that mediates experimental allergic neuritis in the Lewis rat in vivo. J. Immunol. 133:1946–1950.

    Google Scholar 

  9. Sheremata, W. A., Rocklin, R. E., and David, J. 1974. Cellular hypersensitivity in Guillain-Barre syndrome. Can. Med. Assoc. J. 110:1245–1247.

    Google Scholar 

  10. Sheremata, W. A., Colby, S., Karkhanis, Y., and Eylar, E. 1975. Cellular hypersensitivity to basic myelin (P2) protein in the Guillian-Barre syndrome. Can. J. Neurol. Sci. 2:87–90.

    Google Scholar 

  11. Lubetzki, I., and Abramsky, O. 1986. Acute and chronic demyelinating inflammatory polyradiculoneuropathy. Arch. Neurol. 43:604–611.

    Google Scholar 

  12. Geczy, C., Raper, R., Roberts, I. M., Meyer, P., and Bernard, C. C. A. 1985. Macrophage procoagulant activity as a measure of cell-mediated immunity to P2 protein of peripheral nerves in the Guillian-Barre syndrome. J. Neurocimmunol 9:179–191.

    Google Scholar 

  13. Hughes, R. A. C., Gray, I. A., Gregson, N. A., Kadlubowski, M., Kennedy, M., Leibowitz, S., and Thompson, H. 1984. Immune response to myelin antigens in Guillain-Barre syndrome. J. Neuroimmunol. 6:303–312.

    Google Scholar 

  14. Iqbal, A., Oger, J. J. F., and Arnason, B. G. W. 1981. Cell mediated immunity in idiopathic polyneuritis. Ann. Neurol. 9:65–75.

    Google Scholar 

  15. Zweiman, B., Rostami, A., Lisak, R. P., Moskovitz, A. R., and Pleasure, D. E. 1983. Immune reactions to P2 protein in human inflammatory demyelinative neuropathies. Neurology 33:234–237.

    Google Scholar 

  16. Taylor, W. A., Brostoff, S. W., and Hughes, R. A. C. 1991. P2 specific lymphocyte transformation in Guillain-Barre syndrome and chronic idiopathic demyelinating polyradiculoneuropathy. J. Neurol. Sci. 104:52–55.

    Google Scholar 

  17. Milner, P., Lovelidge, C. A., Taylor, W. A., and Hughes, R. A. C. 1987. PO myelin protein produces experimental allergic neuritis in Lewis rats. J. Neurol. Sci. 79:275–285.

    Google Scholar 

  18. Linington, C., Lassmann, H., Kosin, S., and Mongan, L. PO Peptide specific T cell lines induce experimental allergic neuritis in the Lewis rat. submitted.

  19. Melnick, S. C., and Flewett, T. H. 1964. The role of infection in the Guillain-Barre syndrome. J. Neurol. Neurosurg. Psych. 27:395–403.

    Google Scholar 

  20. Arnason, B. G. W. 1984. Inflammatory polyradiculoneuropathies. In: Dyck, P. J., Thomas, P. K., Lambert, E. H. (eds.) Peripheral Neuropathy, Saunders, Philadelphia, pp. 2050–2100.

    Google Scholar 

  21. Jahnke, U., Fischer, E. H., and Alvord, E. C. 1985. Sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis. Science 229:282–284.

    Google Scholar 

  22. Fujinami, R. S., and Oldstone, M. P. A. 1985. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity. Science 230:1043–1045.

    Google Scholar 

  23. Singh, V. K., Yamaki, K., Donoso, L. A., and Shinohara, T. 1989. Molecular mimicry. Yeast histone H3-induced experimental autoimmune uveitis. J. Immunol. 142:1512–1518.

    Google Scholar 

  24. Boucquey, D., and Sindic, C. J. M., Lamy, M., Delmee, M., Tomasi, J. P., and Laterre, E. C. 1991. Clinical and serological studies in a series of 45 patients with Guillain-Barre syndrome. J. Neurol. Sci. 104:56–63.

    Google Scholar 

  25. Dowling, P. C., and Cook, S. D. 1981. Role of infection in Guillain barre syndrome. Laboratory confirmation of herpes viruses in 41 cases. Ann. Neurol [Suppl]9:44–55

    Google Scholar 

  26. Sanders, E. A. C. M., Peters, A. C. B., Gratana, J. W., and Hughes, R. A. C. 1987. Guillain-Barre syndrome after varicellazoster infection. J. Neurology 234:437–439.

    Google Scholar 

  27. Pearson, W. R., and Lipman, D. J. 1988. Improved tools for biological sequence comparisons. Proc. Natl. Acad. Sci. USA 85:2444–2453.

    Google Scholar 

  28. Lemke, G., and Axel, R. 1985. Isolation and sequence of a cDNA encoding the major structural protein of peripheral nerve myelin. Cell 40:501–509.

    Google Scholar 

  29. Margalit, H., Spouge, J. L., Cornette, J. L., Cease, K. B., Delisio, C., and Berzofsky, J. A. 1987. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J. Immunol. 138:2213–2229.

    Google Scholar 

  30. Baer, R., Bankier, A. T., Biggin, M. D., et al. 1985. DnA sequence and expression of the B95-8 Epstein Barr virus genome. Nature 310:207–211.

    Google Scholar 

  31. Weston, K., and Barrell, B. G. 1986. Sequence of the short unique region, short repeats and part of the long repeats of human cytomegalovirus. J. Mol. Biol. 192:177–208.

    Google Scholar 

  32. Chee, M. S., Bankier, A. T., Beck, S., et al. 1990. Analysis of the protein coding content of the human cytomegalovirus strain AD169. Curr. Top. Microbiol. Immunol. 154:125–138.

    Google Scholar 

  33. Pieniazek, N. J., Siemenda, S. B., Pieniazek, D., Velarde, J., Jr., and Luftig, R. B. 1990. Human entric adenovirus type 41 (Tak) contains a second fibre protein gene. Nucleic Acid Research. 18:1901–1912.

    Google Scholar 

  34. Alestrom, P., Akusjarvi, G., Pettersson, M., and Pettersson, U. 1982. DNA sequence analysis of the region encoding the terminal protein and hypothetical N-gene product of Adenovirus type 2. J. Biol. Chem. 257:13492–13499.

    Google Scholar 

  35. Cheng-Mayer, C., Quiroga, M., Tung, J. W., Dina, D., and Levy, J. 1990. Viral determinants of human immunodeficiency virus Type 1, T cell or macrophage tropism, cytopathogenicity and CD4 antigen modulation. J. Virol. 64:4390–4398.

    Google Scholar 

  36. Davison, A. J., and Scott, J. E. 1986. The complete DNA sequence of varicella zoster virus. J. Gen. Virol. 67:1759–1816.

    Google Scholar 

  37. Tarlow, O., McCorquodale, J. G., and McCrae, M. A. 1988. Molecular cloning and sequencing of the gene (M2) encoding the major virion structural protein of serotypes 1 and 3 of mammalian reovirus. Virology 164:141–146.

    Google Scholar 

  38. Kaldor, J., and Speed, B. R. 1984. Guillain-Barre syndrom and campylobacter jejuni: a serological study. Br. Med. J. 1867–1870.

  39. Johnson, R. T. 1982. Parainfectious neurological syndromes. Pages 169–200,in Johnson R. T. (ed.) Viral infections of the nervous system. Raven Press, New York.

    Google Scholar 

  40. Dalakos, and Pezeshkpour. 1988. Ann. Neurol. 23 (Suppl): 538–548.

    Google Scholar 

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Special issue dedicated to Dr. Alan N. Davison

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Adelmann, M., Linington, C. Molecular mimicry and the autoimmune response to the peripheral nerve myelin PO glycoprotein. Neurochem Res 17, 887–891 (1992). https://doi.org/10.1007/BF00993264

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