Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparison with MOG N-terminal peptide sequence. As expected, MOG mRNA expression is CNS-specific and peaks during active myelination. Our studies show that full length MOG mRNA is approximately 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N-glycosylation is found at Asn-31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N-terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B-G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig-like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members.
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PMID:Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily. 145 82

Myelin/oligodendrocyte glycoprotein (MOG) is a CNS-specific protein that has been identified on the external myelin sheath and oligodendrocyte processes. MOG is the primary target autoantigen for demyelinating antibodies in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated a number of rat MOG cDNA clones as tools to begin studies to ascertain MOG function. A full-length cDNA clone (1.6 kb) was sequenced and the amino acid sequence for MOG deduced. This cDNA clone encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24962 MW). A single site for N-glycosylation is found at Asn-31. The N-terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor, and 39% identity with chicken B-G antigen, a major histocompatibility complex antigen. This homology with Ig-like chicken MHC B-G antigens raises the issue of MOG involvement in autoimmune demyelination. Both MOG and butyrophilin meet criteria for inclusion in the immunoglobulin gene superfamily. Moreover, MOG appears to represent a novel member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of this superfamily. MOG mRNA expression is restricted to CNS tissue, and peak expression occurs during active myelination.
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PMID:Cloning and cDNA sequence analysis of myelin/oligodendrocyte glycoprotein: a novel member of the immunoglobulin gene superfamily. 768 65

Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. We have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. We colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC.
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PMID:Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex. 836 42

Experimental autoimmune encephalomyelitis (EAE) induced by sensitization with myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmune disease that reproduces the inflammatory demyelinating pathology of multiple sclerosis. We report that an encephalitogenic T cell response to MOG can be either induced or alternatively suppressed as a consequence of immunological cross-reactivity, or "molecular mimicry" with the extracellular IgV-like domain of the milk protein butyrophilin (BTN). In the Dark Agouti rat, active immunization with native BTN triggers an inflammatory response in the CNS characterized by the formation of scattered meningeal and perivascular infiltrates of T cells and macrophages. We demonstrate that this pathology is mediated by a MHC class II-restricted T cell response that cross-reacts with the MOG peptide sequence 76-87, I GEG KVA LRIQ N (identities underlined). Conversely, molecular mimicry with BTN can be exploited to suppress disease activity in MOG-induced EAE. We demonstrate that not only is EAE mediated by the adoptive transfer of MOG74-90 T cell lines markedly ameliorated by i.v. treatment with the homologous BTN peptide, BTN74-90, but that this protective effect is also seen in actively induced disease following transmucosal (intranasal) administration of the peptide. These results identify a mechanism by which the consumption of milk products may modulate the pathogenic autoimmune response to MOG.
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PMID:Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. 1094 19

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although the etiology of MS remains unknown, studies in experimental autoimmune encephalomyelitis (EAE) have suggested that foreign molecules, which show molecular mimicry with myelin antigens, may play an important role as causative agents of the human disease. In this study, we investigate the molecular mimicry between the extracellular Ig-like domain of the cow's milk protein butyrophilin (BTN) and the extracellular domain of myelin oligodendrocyte glycoprotein (MOG), a candidate autoantigen in MS. Interestingly, we found that as a result of a non-pathogenic cross-reactivity that is localized to a subdominant region of MOG, treatment of C57BL/6 mice with BTN either before or after immunization with MOG was shown to prevent and also suppress the clinical manifestations of EAE. BTN treatment resulted in a significant reduction in both proliferation and production of Th1-related cytokines (IFN-gamma, IL-2, IL-12 and granulocyte macrophage colony stimulating factor) in response to MOG. This specific inhibition was consistently associated with an up-regulation in IL-10 secretion. Furthermore, adoptive transfer of BTN-specific T cells prior to active immunization with MOG resulted in a transitory reduction of the clinical symptoms. Our results suggest that the clinical improvement associated with BTN treatment involved the combination of both anergy and regulatory cells secreting high levels of IL-10. In conclusion, we show that despite the traditional link between molecular mimicry and pathogenic immune response, environmental agents that share homology with autoantigens may also represent a source of cells with a protective phenotype.
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PMID:Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin. 1497 22

Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II expression, suggesting a role in T cell immunity. To address this, we generated Btn2a2-deficient mice. Btn2a2(-/-) mice exhibited enhanced effector CD4(+) and CD8(+) T cell responses, impaired CD4(+) regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis. Altered immune responses were attributed to Btn2a2 deficiency in antigen-presenting cells rather than T cells or nonhematopoietic cells. These results provide the first genetic evidence that BTN2A2 is a co-inhibitory molecule that modulates T cell-mediated immunity.
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PMID:Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes. 2680 44