title: A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes.
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.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Conrad
authors.forename: R N
authors.initials: RN
authors.lastname: Weissmahr
authors.forename: J
authors.initials: J
authors.lastname: Böni
authors.forename: R
authors.initials: R
authors.lastname: Arcari
authors.forename: J
authors.initials: J
authors.lastname: Schüpbach
authors.forename: B
authors.initials: B
authors.lastname: Mach
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D016679:Genome, Viral; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000145:classification / Q000201:enzymology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010802:Phylogeny; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D018089:Superantigens / Q000235:genetics* / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; C107453:ERVK-18 protein, human; C084778:M12 protein, Mouse mammary tumor virus; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018089:Superantigens; D014759:Viral Envelope Proteins; D012194:RNA-Directed DNA Polymerase