Monoclonal antibody to Theiler's murine encephalomyelitis virus defines a determinant on myelin and oligodendrocytes, and augments demyelination in experimental allergic encephalomyelitis.
Theiler's murine encephalomyelitis virus (TMEV) causes a chronic demyelinating disease in mice. The mechanisms underlying the demyelination have not been fully elucidated. We have raised a mAb to TMEV (DA strain), H8, that reacts both with TMEV VP-1 and galactocerebroside (GC). In mouse brain cultures, cells positive for the mAb H8 epitope were double labeled with antibody to myelin basic protein, indicating that those cells were oligodendrocytes. Further, mAb H8 could immunostain myelin structures in frozen sections from mouse brains. When injected intravenously into mice with acute allergic encephalomyelitis, mAb H8 increased by 10-fold the size of demyelinated areas within the spinal cords. This is the first report demonstrating that an antibody to virus can enhance demyelination of a central nervous system disease. Ig fractions from the sera of mice with chronic TMEV infection had antibody(s) to GC, as well as to TMEV, as determined by ELISA. Furthermore, a competition ELISA for TMEV or GC antigen revealed that sera from these infected mice contained antibody(s) with the same specificity as mAb H8. Our results indicate that antibodies generated by immune response to TMEV can react with myelin and oligodendrocytes, and contribute to demyelination through an immune process.
Department of Pathology, University of California, San Diego, La Jolla 92093.
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M
Yamada
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A
Zurbriggen
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RS
Fujinami
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D004770:Enterovirus / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D004680:Maus Elberfeld virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009185:Myelin Proteins / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology*; D013116:Spinal Cord / Q000473:pathology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D009185:Myelin Proteins