Elsevier

Journal of Neuroimmunology

Volume 63, Issue 1, 1 December 1995, Pages 17-27
Journal of Neuroimmunology

Research paper
The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat

https://doi.org/10.1016/0165-5728(95)00124-7Get rights and content

Abstract

Using a highly purified recombinant protein, mMOG, we demonstrate that autoimmune responses to the N-terminal domain (a.a. 1–125) of the myelin oligodendrocyte glycoprotein (MOG) induce an acute demyelinating variant of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Immunisation with 100 μg of mMOG in adjuvant at the base of the tail induced mild clinical disease in 9 of 11 animals (mean clinical score 1.1). The disease was characterised histopathologically by the presence of inflammation and focal demyelinating lesions in the central nervous system (CNS). Adoptive transfer experiments suggest that this inflammatory demyelinating pathology is mediated by synergy between a weakly encephalitogenic, MOG-specific T cell response and a demyelinating, MOG-specific autoantibody response. Using in vitro selected mMOG-reactive T cell lines, the encephalitogenic T cell response to this domain of MOG was found to recognise two distinct epitopes, MOG1–20 and MOG35–55; whereas ELISA demonstrated that the immunodominant B cell epitope was located within the amino acid sequence MOG1–25. However although active immunisation with synthetic peptides corresponding to the T cell epitopes, MOG1–20 or MOG35–55, induced an inflammatory response in the CNS, this was not associated with demyelination indicating that the demyelinating antibody response recognises other, possibly conformation dependent epitopes. This study unequivocally demonstrates that MOG-specific autoimmune responses are alone sufficient to induce a demyelinating disease of the CNS and supports the proposal that MOG may play an important role in the immunopathogenesis of multiple sclerosis.

References (26)

  • N. Kerlero de Rosbo et al.

    Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/oligodendrocyte glycoprotein

    J. Neurochem.

    (1990)
  • N. Kerlero de Rosbo et al.

    Reactivity to myelin antigens in multiple sclerosis

    J. Clin. Invest.

    (1993)
  • K. Kojima et al.

    Experimental autoimmune panencephalitis and uveoretinitis in the Lewis rat transferred by T lymphocytes specific for the S100b molecule, a calcium binding protein of astroglia

    J. Exp. Med.

    (1994)
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