Tg. Johns et Cca. Bernard, BINDING OF COMPLEMENT COMPONENT CLQ TO MYELIN OLIGODENDROCYTE GLYCOPROTEIN - A NOVEL MECHANISM FOR REGULATING CNS INFLAMMATION, Molecular immunology, 34(1), 1997, pp. 33-38
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.