Structure & Function Of Myelin Oligodendrocyte Glycoprotein

  1. Pathogenic Myelin Oligodendrocyte Glycoprotein Antibodies recognize glycosylated Epitopes and perturb Oligodendrocyte physiology
    Proc Natl Acad Sci USA 2005 Sep 27;102(39):13992-7

  2. Anti-Myelin AntiBodies do not allow earlier diagnosis of Multiple Sclerosis
    Mult Scler 2005 Aug;11(4):492-4

  3. Tolerance induction by Bone Marrow Transplantation in a Multiple Sclerosis model
    Blood 2005 May 17

  4. AutoAntiBody synthesis in Primary/Progressive Multiple Sclerosis patients treated with Interferon-beta-1b
    J Neurol 2004 Dec;251(12):1498-501

  5. HLA-DRB1*1501 risk association in Multiple Sclerosis may not be related to presentation of Myelin Epitopes
    J NeuroSci Res 2004 Oct 1;78(1):100

  6. In vitro evidence that ImmunuAffinity-purified MOG contains ImmunoGenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG
    J NeuroImmunol 2001 Aug 30;118(2):194-202

  7. Conformational analysis of a GlycoSylated human Myelin Oligodendrocyte Glycoprotein peptide epitope able to detect AntiBody response in Multiple Sclerosis
    J Med Chem 2001 Jul 5;44(14):2378-81

  8. No association between anti-Myelin Oligodendrocyte Glycoprotein AntiBodies and Serum/CerebroSpinal Fluid levels of the soluble InterLeukin-6 receptor complex in Multiple Sclerosis
    NeuroSci Lett 2001 Jun 1;305(1):13-6

  9. Immune responses against the Myelin/Oligodendrocyte GlycoProtein in Experimental AutoImmune DeMyelination
    J Clin Immunol 2001 May;21(3):155-70

  10. Insights into the Etiology and PathoGenesis of Multiple Sclerosis
    Immunol Cell Biol 1998 Feb;76(1):47-54

  1. AntiBody cross-reactivity between Myelin Oligodendrocyte Glycoprotein and the milk protein Butyrophilin in Multiple Sclerosis
    J Immunol 2004 Jan 1;172(1):661-

  2. The crystal structure of Myelin Oligodendrocyte Glycoprotein, a key AutoAntigen in Multiple Sclerosis
    Proc Natl Acad Sci USA 2003 Sep 16;100(19):11059-64

  3. T-Cell Epitopes of human Myelin Oligodendrocyte Glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are Encephalitogenic and are presented by human B-Cells
    J Immunol 2001 Dec 15;167(12):7119-25

  4. Structure & function of Myelin Oligodendrocyte Glycoprotein
    J NeuroChem 1999 Jan;72(1):1-9


AntiBody cross-reactivity between Myelin Oligodendrocyte Glycoprotein and the milk protein Butyrophilin in Multiple Sclerosis

Guggenmos J, Schubart AS, Ogg S, Andersson M, Olsson T, Mather IH, Linington C
J Immunol 2004 Jan 1;172(1):661-8
Max Planck Institute of NeuroBiology, Department of NeuroImmunology, Martinsried, Germany
PMID# 14688379

The Etiology of Multiple Sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown.

In this study, we demonstrate that Ab specific for the ExtraCellular Ig-like domain of Myelin Oligodendrocyte Glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein Butyrophilin (BTN).

Analysis of paired samples of MS Sera and CerebroSpinal Fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its Epitope specificity from that in the periphery.

This effect was statistically significant for the Ab response to BTN(76-100) (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG Peptide MOG(76-100) in 34% of MS patients (n = 35).

These observations suggested that Intrathecal synthesis of Ab recognizing BTN Peptide Epitopes in the CNS was sustained by molecular mimicry with MOG.

Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific AutoAntibodies ImmunoPurified from MS Sera.

The MOG-specific Ab repertoire cross-reacts with multiple BTN Peptide Epitopes including a MOG/BTN(76-100)-specific component that occurred at a higher frequency in MS patients than in SeroPositive healthy controls.

As well as responses to Epitopes within MOG/BTN(1-39) that occur at similar frequencies in both groups.

The demonstration of Molecular Mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific AutoImmune repertoire during the course of MS.


The Crystal Structure Of Myelin Oligodendrocyte Glycoprotein, A Key AutoAntigen In Multiple Sclerosis

Clements CS, Reid HH, Beddoe T, Tynan FE, Perugini MA, Johns TG, Bernard CC, Rossjohn J
Proc Natl Acad Sci USA 2003 Sep 16;100(19):11059-64
Monash University, School of Biomedical Sciences, Department of BioChemistry and Molecular Biology, Protein Crystallography Unit, Clayton, Victoria 3168, Australia
PMID# 12960396

Myelin Oligodendrocyte Glycoprotein (MOG) is a key CNS-specific AutoAntigen for primary DeMyelination in Multiple Sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure.

To gain new insights into the physiological and ImmunoPathological role of MOG, we determined the 1.8-A crystal structure of the MOG ExtraCellular Domain (MOGED).

MOGED adopts a classical Ig (Ig variable domain) fold that was observed to form an antiparallel head-to-tail dimer.

A dimeric form of native MOG was observed, and MOGED was also shown to dimerize in solution, consistent with the view of MOG acting as a homophilic Adhesion Receptor.

The MOG35-55 peptide, a major Encephalitogenic determinant recognized by both T-Cells and DeMyelinating AutoAntiBodies, is partly occluded within the dimer interface.

The structure of this key AutoAntigen suggests a relationship between the dimeric form of MOG within the Myelin sheath and a breakdown of Immunological Tolerance to MOG that is observed in Multiple Sclerosis.


T-Cell Epitopes Of Human Myelin Oligodendrocyte Glycoprotein Identified In HLA-DR4 (DRB1*0401) Transgenic Mice Are Encephalitogenic And Are Presented By Human B-Cells

Forsthuber TG, Shive CL, Wienhold W, de Graaf K, Spack EG, Sublett R, Melms A, Kort J, Racke MK, Weissert R
J Immunol 2001 Dec 15;167(12):7119-25
Case Western Reserve University, School of Medicine, Institute of Pathology, Cleveland, OH 44106, USA
PMID# 11739534

Myelin Oligodendrocyte Glycoprotein (MOG) is an Ag present in the Myelin sheath of the CNS thought to be targeted by the AutoImmune T-Cell response in Multiple Sclerosis (MS).

In this study, we have for the first time characterized the T-Cell Epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC Class II Allele associated with MS in a subpopulation of patients.

Using MHC binding algorithms, we have predicted MOG Peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T-Cell reactivity to overlapping MOG Peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG.

The data indicated that MOG Peptide 97-108 (core 99-107, FFRDHSYQE) was the Immunodominant HLA-DR4-restricted T-Cell Epitope in vivo.

This Peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe Experimental Autoimmune Encephalomyelitis in the HLA-DR4 transgenic mice.

Interestingly, the same Peptide was presented by human B-Cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG Epitopes in the pathogenesis of human MS.


Structure & Function Of Myelin Oligodendrocyte Glycoprotein

Johns TG, Bernard CC
J NeuroChem 1999 Jan;72(1):1-9
LaTrobe University, NeuroImmunology Laboratory, Bundoora, Victoria, Australia
UI# 9886048; UI# 99101139

Myelin Oligodendrocyte Glycoprotein (MOG) is a quantitatively minor component of CNS Myelin whose function remains relatively unknown.

As MOG is an AutoAntigen capable of producing a DeMyelinating Multiple Sclerosis like disease in mice and rats, much of the research directed toward MOG has been Immunological in nature.

Although the function of MOG is yet to be elucidated, there is now a relatively large amount of Biochemical and Molecular data relating to MOG.

Here we summarize this information and include our recent findings pertaining to the cloning of the Marsupial MOG gene. On the basis of this knowledge we suggest three possible functions for MOG:

  1. Cellular Adhesive Molecule
  2. Regulator of Oligodendrocyte MicroTubule stability
  3. Mediator of interactions between Myelin and the Immune System, in particular, the Complement Cascade

Given that AntiBodies to MOG and to the Myelin Specific Glycolipid (Gal-C) both activate the same signaling pathway leading to MBP degradation, we propose that there is a direct interaction between the Membrane associated regions of MOG and Gal-C.

Such an interaction may have important consequences regarding the Membrane Topology and Function of both Molecules.

Finally, we examine how Polymorphisms and/or mutations to the MOG Gene could contribute to the PathoGenesis of Multiple Sclerosis.

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