
DOI . ORG {
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Title[redir]:
Myelin oligodendrocyte glycoprotein: a novel candidate autoantigen in multiple sclerosis | Journal of Molecular Medicine
Description:
โMyelin oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin superfamily expressed exclusively in central nervous system (CNS) myelin. While the function of MOG is unknown, a number of studies have shown that immune responses to MOG contribute to the autoimmune-mediated demyelination seen in animals immunized with whole CNS tissue. This paper summarizes our recent studies, which unequivocally demonstrate that MOG by itself is able to generate both an encephalitogenic T cell response and an autoantibody response in Lewis rats and in several strains of mice. In Lewis rats the injection of both native MOG and MOG35โ55 peptide produces a paralytic relapsing-remitting neurological disease with extensive plaque-like demyelination. The antibody response to MOG35โ55 was highly restricted, as no reactivity to either other MOG peptides or myelin proteins could be detected. Fine epitope mapping showed that antibody from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37โ46, which is contiguous to the dominant T cell epitope contained within MOG44โ55. NOD/Lt and C57BL/6 mice were also susceptible to severe neurological disease following injection with recombinant MOG or MOG35โ55 peptide, indicating that this specific CNS autoantigen, or some of its determinants, can induce a pathogenic response across animal species. Severe paralysis and extensive demyelination were seen in both strains, but NOD/Lt mice experienced a chronic relapsing disease whereas C57BL/6 mice had a chronic non-remitting disease. Moreover, transfer of MOG35โ55 T cells into naive NOD/Lt mice also produced severe neurological impairment as well as histological lesions. These results emphasize that a synergism between a T cell-response and anti-MOG antibodies may be important for the development of severe demyelinating disease. This, together with our demonstration that there is a predominant T cell response to MOG in patients with multiple sclerosis, clearly indicates that MOG is probably an important target autoantigen in this disease.
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Keywords {๐}
mog, article, myelin, disease, access, oligodendrocyte, response, privacy, cookies, content, journal, glycoprotein, autoantigen, multiple, sclerosis, demyelination, mice, information, publish, search, cns, severe, antibodies, autoimmune, open, data, log, research, bernard, johns, slavin, cell, rats, neurological, nodlt, discover, springer, function, optional, personal, parties, policy, find, track, molecular, medicine, candidate, cite, ichikawa, ewing,
Topics {โ๏ธ}
human autoimmune encephalomyelitis myelin-reactive antibodies initiate myelin oligodendrocyte glycoprotein autoimmune-mediated demyelination month download article/chapter nod/lt mice experienced naive nod/lt mice multiple sclerosis molecular medicine aims related subjects privacy choices/manage cookies full article pdf anti-mog antibodies specific cns autoantigen severe neurological disease important target autoantigen check access instant access cell epitope contained chronic relapsing disease severe demyelinating disease european economic area scope submit manuscript central nervous system la trobe university conditions privacy policy accepting optional cookies extensive demyelination journal finder publish article journal mog35โ55 peptide produces myelin proteins pathogenic immune response article log candidate autoantigen nod/lt remitting disease article cite article bernard demyelination privacy policy personal data books a myelin optional cookies manage preferences severe paralysis cell response cell-response journal publish
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headline:Myelin oligodendrocyte glycoprotein: a novel candidate autoantigen in multiple sclerosis
description:โMyelin oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin superfamily expressed exclusively in central nervous system (CNS) myelin. While the function of MOG is unknown, a number of studies have shown that immune responses to MOG contribute to the autoimmune-mediated demyelination seen in animals immunized with whole CNS tissue. This paper summarizes our recent studies, which unequivocally demonstrate that MOG by itself is able to generate both an encephalitogenic T cell response and an autoantibody response in Lewis rats and in several strains of mice. In Lewis rats the injection of both native MOG and MOG35โ55 peptide produces a paralytic relapsing-remitting neurological disease with extensive plaque-like demyelination. The antibody response to MOG35โ55 was highly restricted, as no reactivity to either other MOG peptides or myelin proteins could be detected. Fine epitope mapping showed that antibody from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37โ46, which is contiguous to the dominant T cell epitope contained within MOG44โ55. NOD/Lt and C57BL/6 mice were also susceptible to severe neurological disease following injection with recombinant MOG or MOG35โ55 peptide, indicating that this specific CNS autoantigen, or some of its determinants, can induce a pathogenic response across animal species. Severe paralysis and extensive demyelination were seen in both strains, but NOD/Lt mice experienced a chronic relapsing disease whereas C57BL/6 mice had a chronic non-remitting disease. Moreover, transfer of MOG35โ55 T cells into naive NOD/Lt mice also produced severe neurological impairment as well as histological lesions. These results emphasize that a synergism between a T cell-response and anti-MOG antibodies may be important for the development of severe demyelinating disease. This, together with our demonstration that there is a predominant T cell response to MOG in patients with multiple sclerosis, clearly indicates that MOG is probably an important target autoantigen in this disease.
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Key wordsโMyelin oligodendrocyte glycoprotein
Multiple sclerosis
Experimental autoimmune encephalomyelitis
Demyelination
Autoantigen
Molecular Medicine
Human Genetics
Internal Medicine
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headline:Myelin oligodendrocyte glycoprotein: a novel candidate autoantigen in multiple sclerosis
description:โMyelin oligodendrocyte glycoprotein (MOG) is a member of the immunoglobulin superfamily expressed exclusively in central nervous system (CNS) myelin. While the function of MOG is unknown, a number of studies have shown that immune responses to MOG contribute to the autoimmune-mediated demyelination seen in animals immunized with whole CNS tissue. This paper summarizes our recent studies, which unequivocally demonstrate that MOG by itself is able to generate both an encephalitogenic T cell response and an autoantibody response in Lewis rats and in several strains of mice. In Lewis rats the injection of both native MOG and MOG35โ55 peptide produces a paralytic relapsing-remitting neurological disease with extensive plaque-like demyelination. The antibody response to MOG35โ55 was highly restricted, as no reactivity to either other MOG peptides or myelin proteins could be detected. Fine epitope mapping showed that antibody from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37โ46, which is contiguous to the dominant T cell epitope contained within MOG44โ55. NOD/Lt and C57BL/6 mice were also susceptible to severe neurological disease following injection with recombinant MOG or MOG35โ55 peptide, indicating that this specific CNS autoantigen, or some of its determinants, can induce a pathogenic response across animal species. Severe paralysis and extensive demyelination were seen in both strains, but NOD/Lt mice experienced a chronic relapsing disease whereas C57BL/6 mice had a chronic non-remitting disease. Moreover, transfer of MOG35โ55 T cells into naive NOD/Lt mice also produced severe neurological impairment as well as histological lesions. These results emphasize that a synergism between a T cell-response and anti-MOG antibodies may be important for the development of severe demyelinating disease. This, together with our demonstration that there is a predominant T cell response to MOG in patients with multiple sclerosis, clearly indicates that MOG is probably an important target autoantigen in this disease.
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Multiple sclerosis
Experimental autoimmune encephalomyelitis
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Autoantigen
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Human Genetics
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