Epitopes described in "A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy."

Article Authors:Cédric Louvet; Beniwende G Kabre; Dan W Davini; Nicolas Martinier; Maureen A Su; Jason J DeVoss; Wendy L Rosenthal; Mark S Anderson; Hélène Bour-Jordan; Jeffrey A Bluestone
Article Title:A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy.
Reference Detail
Reference ID:1014233
Abstract:Autoimmune-prone nonobese diabetic mice deficient for B7-2 spontaneously develop an autoimmune peripheral neuropathy mediated by inflammatory CD4(+) T cells that is reminiscent of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. To determine the etiology of this disease, CD4(+) T cell hybridomas were generated from inflamed tissue-derived CD4(+) T cells. A majority of T cell hybridomas were specific for myelin protein 0 (P0), which was the principal target of autoantibody responses targeting nerve proteins. To determine whether P0-specific T cell responses were sufficient to mediate disease, we generated a novel myelin P0-specific T cell receptor transgenic (POT) mouse. POT T cells were not tolerized or deleted during thymic development and proliferated in response to P0 in vitro. Importantly, when bred onto a recombination activating gene knockout background, POT mice developed a fulminant form of peripheral neuropathy that affected all mice by weaning age and led to their premature death by 3-5 wk of age. This abrupt disease was associated with the production of interferon gamma by P0-specific T cells and a lack of CD4(+) Foxp3(+) regulatory T cells. Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy.
Affiliations:Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Reference Type:Literature
PubMed ID:19221395
Journal:J Exp Med
Journal Volume:206
Article Pages:507-14
Journal ISSN:0022-1007
Article Chemical List:Cytokines;Epitopes;Myelin P0 Protein;Receptors, Antigen, T-Cell, alpha-beta
Article MeSH List:Animals; Autoimmune Diseases(complications; immunology; pathology); CD4-Positive T-Lymphocytes(immunology); Cell Proliferation; Cytokines(biosynthesis); Epitopes; Hybridomas; Mice; Mice, Inbred NOD; Mice, Transgenic; Myelin P0 Protein(metabolism); Peripheral Nerves(immunology; pathology); Peripheral Nervous System Diseases(complications; immunology; pathology); Phenotype; Receptors, Antigen, T-Cell, alpha-beta(immunology)
Curation Last Updated:2015-07-30 20:29:26