BINDING OF COMPLEMENT COMPONENT CLQ TO MYELIN OLIGODENDROCYTE GLYCOPROTEIN - A NOVEL MECHANISM FOR REGULATING CNS INFLAMMATION

Myelin oligodendrocyte glycoprotein (MOG) is a myelin-specific protein restricted to the central nervous system (CNS). While MOG is consider ed a putative autoantigen in MS, its function(s) in myelin is unknown. As CNS myelin is able to activate the classical complement pathway, i t must contain a C1q-binding/activating protein but the identity of th is protein has not been reported. The data in this paper clearly demon strate that MOG specifically binds C1q in a dose-dependent and saturat ing manner. This calcium-dependent interaction is mediated by the extr acellular immunoglobulin-like domain of MOG. This MOG domain contains an amine acid motif similar to the core C1q-binding sequence previousl y identified in IgG antibodies. Purified MOG also inhibited the antibo dy-dependent lysis of RBC by complement. Taken together, these results demonstrate that MOG binds C1q near the IgG binding site and may be t he protein responsible for complement activation in myelin. This direc t interaction between a myelin-specific protein and C1q has significan t implications for CNS inflammation and could be particularly importan t in demyelinating diseases such as multiple sclerosis. (C) 1997 Publi shed by Elsevier Science Ltd.