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      A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes.

      Cell
      Adolescent, Adult, Amino Acid Sequence, Antibodies, Viral, immunology, Autoantibodies, B-Lymphocytes, cytology, Base Sequence, Cells, Cultured, Child, Child, Preschool, Diabetes Mellitus, Type 1, genetics, virology, Genome, Viral, Humans, Infant, Infant, Newborn, Islets of Langerhans, Mammary Tumor Virus, Mouse, classification, enzymology, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Phylogeny, RNA-Directed DNA Polymerase, metabolism, Superantigens, Viral Envelope Proteins

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          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.

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