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

Cell. 1997 Jul 25;90(2):303-13. doi: 10.1016/s0092-8674(00)80338-4.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies, Viral
  • Autoantibodies
  • IDDMK1,2 22 superantigen, human
  • M12 protein, Mouse mammary tumor virus
  • Membrane Glycoproteins
  • Membrane Proteins
  • Superantigens
  • Viral Envelope Proteins
  • RNA-Directed DNA Polymerase

Associated data

  • GENBANK/AF012327
  • GENBANK/AF012328
  • GENBANK/AF012329
  • GENBANK/AF012330
  • GENBANK/AF012331
  • GENBANK/AF012332
  • GENBANK/AF012333
  • GENBANK/AF012334
  • GENBANK/AF012335
  • GENBANK/AF012336
  • GENBANK/AF012337