Abstract
Microbial superantigens (SAGs) have been implicated in the pathogenesis of human autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor positive T cell subset in patients suffering from acute-onset type I diabetes has indicated the presence of a surface membrane-bound SAG. Here, we have isolated a novel mouse mammary tumor virus-related human endogenous retrovirus. We further show that the N-terminal moiety of the envelope gene encodes an MHC class II-dependent SAG. We propose that expression of this SAG, induced in extrapancreatic and professional antigen-presenting cells, leads to beta-cell destruction via the systemic activation of autoreactive T cells. The SAG encoded by this novel retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Amino Acid Sequence
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Antibodies, Viral / immunology
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Autoantibodies / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology
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Base Sequence
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Cells, Cultured
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Child
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Child, Preschool
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Diabetes Mellitus, Type 1 / genetics*
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 1 / virology
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Genome, Viral
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Humans
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Infant
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Infant, Newborn
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Islets of Langerhans / immunology
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Islets of Langerhans / virology
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Mammary Tumor Virus, Mouse / classification
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Mammary Tumor Virus, Mouse / enzymology
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Mammary Tumor Virus, Mouse / immunology*
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Membrane Glycoproteins / immunology
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Membrane Proteins
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Molecular Sequence Data
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Phylogeny
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RNA-Directed DNA Polymerase / metabolism
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Superantigens / genetics*
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Superantigens / immunology*
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Viral Envelope Proteins / immunology
Substances
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Antibodies, Viral
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Autoantibodies
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ERVK-18 protein, human
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M12 protein, Mouse mammary tumor virus
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Membrane Glycoproteins
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Membrane Proteins
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Superantigens
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Viral Envelope Proteins
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RNA-Directed DNA Polymerase
Associated data
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GENBANK/AF012327
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GENBANK/AF012328
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GENBANK/AF012329
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GENBANK/AF012330
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GENBANK/AF012331
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GENBANK/AF012332
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GENBANK/AF012333
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GENBANK/AF012334
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GENBANK/AF012335
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GENBANK/AF012336
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GENBANK/AF012337