Epitope specificity of demyelinating monoclonal autoantibodies directed against the human myelin oligodendrocyte glycoprotein (MOG).
We describe the epitope specificity of a panel of ten demyelinating monoclonal antibodies (mAb) that recognise the extracellular immunoglobulin-like domain of human myelin oligodendrocyte glycoprotein (hMOG(lgd)). All the mAbs bind to the surface of MOG-transfected fibroblasts as assessed in vitro by FACS and immunocytochemistry but failed to recognise overlapping 15-mer MOG peptides when assessed by ELISA. However, increasing peptide length to 25 amino acids revealed that four mAbs recognised epitopes within the amino acid sequence 63-100 of human MOG. In contrast, a non-demyelinating MOG-specific mAb recognised MOG by both ELISA and Western blotting but failed to stain MOG transfected fibroblasts. These observations suggest that assays based on the use of MOG-transfected cell lines will differentiate between pathogenic and non-pathogenic MOG-specific antibody responses in experimental models and human diseases of the nervous system.
Brehm
U
U
Max-Planck-Institute of Neurobiology, Department of Neuroimmunology, Martinsried, Germany. brehm@neuro.mpg.de
Piddlesden
S J
SJ
Gardinier
M V
MV
Linington
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000737:chemistry* / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011994:Recombinant Proteins