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International Immunology, Vol. 15, No. 12, pp. 1473-1483, December 2003
© 2003 Japanese Society for Immunology

Autoantibodies and CD4 T cells target a ß cell retroviral envelope protein in non-obese diabetic mice

Matteo G. Levisetti1,2, Anish Suri1, Ilan Vidavsky3, Michael L. Gross3, Osami Kanagawa1 and Emil R. Unanue1

1 Department of Pathology and Immunology, and 2 Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA 3 Department of Chemistry, Washington University, St Louis, MO 63110, USA

Correspondence to: E. R. Unanue; E-mail: unanue{at}pathbox.wustl.edu
Transmitting editor: A. Weiss

We determined that, over a biologic time interval, from 4 to 8 weeks of age, female non-obese diabetic (NOD) mice develop antibodies against pancreatic ß-cell-surface antigens depending upon the presence of both the MHC class II susceptibility allele, I-Ag7, and other NOD background genes. We generated a mAb from a pre-diabetic NOD mouse that binds to the surface of insulinoma cells and isolated mouse ß cells, and identified the target as a retroviral envelope glycoprotein expressed on pancreatic ß cells. The cloned and expressed sequence for this protein was recognized by the mAb. The antibody as well as sera from pre-diabetic NOD mice recognized the recombinant protein. Spontaneous T cell reactivity against a peptide from the cloned protein was found in NOD mice. In conclusion, a ß cell retroviral envelope protein is a target antigen that is selected by the NOD mouse immune system early in the pathogenesis of autoimmune diabetes.

Keywords: autoimmunity, diabetes mellitus, Ig, islets of Langerhans, T lymphocyte


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