A novel myelin-associated glycoprotein defined by a mouse monoclonal antibody

Linnington, Christopher; Webb, M.; Woodhams, P.L.

doi:10.1016/0165-5728(84)90064-x

Cited by 295 publications

(205 citation statements)

References 14 publications

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“…The variable region of the L-chain gene was cloned from the MOG-specific hybridoma clone 8.18C5 (7) and inserted in an expression vector including the C region, the intron enhancer, and the 3Ј-enhancer. A 1.7-kb SacI fragment of genomic DNA containing the rearranged V mog gene was subcloned from a larger clone isolated from a genomic phage library of the hybridoma 8.18C5.…”

Section: Transgenic Micementioning

confidence: 99%

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Development of Myelin Oligodendrocyte Glycoprotein Autoreactive Transgenic B Lymphocytes: Receptor Editing In Vivo After Encounter of a Self-Antigen Distinct from Myelin Oligodendrocyte Glycoprotein

Litzenburger

Blüthmann

Morales

et al. 2000

The Journal of Immunology

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We explored mechanisms involved in B cell self-tolerance against brain autoantigens in a double-transgenic mouse model carrying the Ig H-chain (introduced by gene replacement) and/or the L-chain κ (conventional transgenic) of the mAb 8.18C5, specific for the myelin oligodendrocyte glycoprotein (MOG). Previously, we demonstrated that B cells expressing solely the MOG-specific Ig H-chain differentiate without tolerogenic censure. We show now that double-transgenic (THκmog) B cells expressing transgenic Ig H- and L-chains are subjected to receptor editing. We show that in adult mice carrying both MOG-specific Ig H- and L-chains, the frequency of MOG-binding B cells is not higher than in mice expressing solely the transgenic Ig H-chain. In fact, in THκmog double-transgenic mice, the transgenic κmog L-chain was commonly replaced by endogenous L-chains, i.e., by receptor editing. In rearrangement-deficient RAG-2− mice, differentiation of THκmog B cells is blocked at an immature stage (defined by the B220lowIgMlowIgD− phenotype), reflecting interaction of the autoreactive B cells with a local self-determinant. The tolerogenic structure in the bone marrow is not classical MOG, because back-crossing THκmog mice into a MOG-deficient genetic background does not lead to an increase in the proportion of MOG-binding B cells. We propose that an as yet undefined self-Ag distinct from MOG cross-reacts with the THκmog B cell receptor and induces editing of the transgenic κmog L-chain in early immature B cells without affecting the pathogenic potential of the remaining MOG-specific B cells. This phenomenon represents a particular form of chain-specific split tolerance.

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Section: Transgenic Micementioning

confidence: 99%

“…It is exclusively localized on the outer surface of the myelin sheath, where it can be readily attacked by specific Ab mediating demyelination (5,6). In addition, the expression of MOG is restricted to the CNS, and it appears late during development of myelin (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Development of Myelin Oligodendrocyte Glycoprotein Autoreactive Transgenic B Lymphocytes: Receptor Editing In Vivo After Encounter of a Self-Antigen Distinct from Myelin Oligodendrocyte Glycoprotein

Litzenburger

Blüthmann

Morales

et al. 2000

The Journal of Immunology

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“…It was identified originally as an immunodominant target for demyelinating autoantibodies in a guinea pig model of experimental autoimmune encephalomyelitis (EAE) (3,4). Subsequently, MOG was shown to induce a variant of EAE that exhibits many of the clinical and pathological characteristics of multiple sclerosis (MS) in both rats and primates.…”

mentioning

confidence: 99%

“…M yelin oligodendrocyte glycoprotein (MOG) 4 is a highly conserved transmembrane myelin protein that is expressed exclusively in the CNS (1,2). It was identified originally as an immunodominant target for demyelinating autoantibodies in a guinea pig model of experimental autoimmune encephalomyelitis (EAE) (3,4).…”

mentioning

confidence: 99%

Demyelinating Myelin Oligodendrocyte Glycoprotein-Specific Autoantibody Response Is Focused on One Dominant Conformational Epitope Region in Rodents

Breithaupt

Schäfer

Pellkofer

et al. 2008

The Journal of Immunology

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Conformational epitopes of myelin oligodendrocyte glycoprotein (MOG) provide a major target for demyelinating autoantibodies in experimental autoimmune encephalomyelitis and recent studies indicate that a similar situation may exist in multiple sclerosis. We recently solved the crystal structure of the extracellular domain of MOG (MOGex) in complex with a Fab derived from the demyelinating mAb 8-18C5 and identified the conformational 8-18C5 epitope on MOG that is dominated by the surface exposed FG loop of MOG. To determine the importance of this epitope with regard to the polyclonal Ab response to MOGex we investigated the effects of mutating His103 and Ser104, the two central amino acids of the FG loop, on Ab binding. Mutation of these two residues reduced binding of a panel of eight demyelinating conformation-dependent mAbs to <20% compared with binding to wild-type MOGex, whereas substitution of amino acids that do not contribute to the 8-18C5 epitope had only a minor effect on Ab binding. The same restriction was observed for the polyclonal MOG-specific Ab response of MOG DNA-vaccinated BALB/c and SJL/J mice. Our data demonstrate that the pathogenic anti-MOG Ab response primarily targets one immunodominant region centered at the FG loop of MOG. Comparison of the structure of MOGex with the structures of related IgV-like domains yields a possible explanation for the focused Ab response.

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“…MOG was originally identified as the antigen recognized by the demyelinating antibodies present in serum of animals immunized with whole-brain homogenate [2] and was later characterized as a 26 kDa to 28-kDa glycoprotein [3]. Given its late expression during myelinogenesis in mammals [4Ϫ6] and its location at the membrane surface of oligodendrocytes and external lamellae of myelin sheaths [4,7], MOG has been proposed to play a role either in the completion and maintenance of myelin sheath [5,8], or in the adhesion of adjacent myelinated tracts [9].…”

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confidence: 99%

Membrane topology of the myelin/oligodendrocyte glycoprotein

Gaspera

Pham-Dinh

Roussel

et al. 1998

European Journal of Biochemistry

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Myelin/oligodendrocyte glycoprotein (MOG), a specific component of the mammalian central nervous system, is located on the surface of the oligodendrocyte plasma membrane and the outermost lamellae of mature myelin; it is expressed during the latter steps of myelinogenesis. It has been shown that MOG may play a pathological role in autoimmune demyelinating diseases of the central nervous system, although its physiological function remains unknown. MOG is an integral membrane glycoprotein with an extracellular immunoglobulin-like domain and two hydrophobic segments which were predicted to be membranespanning on the basis of hydropathy analysis. As a first step in elucidation of MOG function, we have investigated its membrane topology, combining immunofluorescence studies on cultured oligodendrocytes and MOG-transfected Chinese hamster ovary cells with biochemical analyses, including in vitro translation, membrane insertion and protease-digestion assays. Our results indicate that the C-terminal tail of MOG is located into the cytoplasm, and that only the first hydrophobic region of MOG spans the membrane whereas the second hydrophobic region appears to be semi-embedded in the lipid bilayer, lying partially buried in the membrane with its N-terminal and C-terminal boundaries facing the cytoplasm.Keywords : MOG; myelin; topology.Central nervous system myelin is synthesized as an extension of the oligodendrocyte plasma membrane, which wraps around axons in a concentric multilamellar sheath. Proteolipid proteins (PLP) and myelin basic proteins (MBP) are the most abundant components [1], accounting for about 80% of the protein. Myelin also contains minor glycoprotein components, such as myelin-associated glycoprotein (MAG) and myelin/oligodendrocyte glycoprotein (MOG).MOG was originally identified as the antigen recognized by the demyelinating antibodies present in serum of animals immunized with whole-brain homogenate [2] and was later characterized as a 26 kDa to 28-kDa glycoprotein [3]. Given its late expression during myelinogenesis in mammals [4Ϫ6] and its location at the membrane surface of oligodendrocytes and external lamellae of myelin sheaths [4,7], MOG has been proposed to play a role either in the completion and maintenance of myelin sheath [5,8], or in the adhesion of adjacent myelinated tracts [9]. However, in vivo and in vitro studies suggested that MOG may be a target autoantigen in autoimmune demyelinating diseases of the central nervous system. In animals with experimental autoimmune encephalomyelitis, an experimental model for multiple sclerosis, the injection of MOG peptides can initiate [12,13] and tolerization assays in a non-human primate model of experimental autoimmune encephalomyelitis led to a lethal encephalopathy [14]. The physiopathological mechanism responsible for this particular and deleterious effect of MOG humoral immunoreactivity may result from the fixation of a component of complement, C1q, to the extracellular domain of MOG [15].Sequence comparison of MOG cDNAs from rat, bovine, ...

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A novel myelin-associated glycoprotein defined by a mouse monoclonal antibody

Cited by 295 publications

References 14 publications

Development of Myelin Oligodendrocyte Glycoprotein Autoreactive Transgenic B Lymphocytes: Receptor Editing In Vivo After Encounter of a Self-Antigen Distinct from Myelin Oligodendrocyte Glycoprotein

Development of Myelin Oligodendrocyte Glycoprotein Autoreactive Transgenic B Lymphocytes: Receptor Editing In Vivo After Encounter of a Self-Antigen Distinct from Myelin Oligodendrocyte Glycoprotein

Demyelinating Myelin Oligodendrocyte Glycoprotein-Specific Autoantibody Response Is Focused on One Dominant Conformational Epitope Region in Rodents

Membrane topology of the myelin/oligodendrocyte glycoprotein

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