Abstract
Increasing evidence implies CD8 T cells in tissue-specific autoimmune diseases including multiple sclerosis. mAbs specific for MHC class I molecules presenting a dominant autoantigenic peptide may allow selective immunotherapy in such settings. We demonstrate the prophylactic and therapeutic efficacy of such a mAb in a transgenic mouse model of lethal demyelinating disease in which a neo-self Ag expressed by oligodendrocytes is targeted by CD8 T cells with transgenic Ag receptors. Mechanistic studies performed in vitro and in vivo indicate that it is the low expression of MHC class I on oligodendrocytes, which makes this form of Ag-specific intervention possible.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Blocking / immunology
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / immunology*
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Autoantigens / immunology*
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Autoimmunity / genetics
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Autoimmunity / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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Coculture Techniques
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Disease Models, Animal
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Flow Cytometry
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Fluorescent Antibody Technique
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / immunology
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Lymphocyte Activation / immunology
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Mice
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Mice, Transgenic
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Microscopy, Confocal
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Multiple Sclerosis / immunology*
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Oligodendroglia / immunology
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Ovalbumin / genetics
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Ovalbumin / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Autoantigens
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Histocompatibility Antigens Class I
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Receptors, Antigen, T-Cell
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Ovalbumin