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

Matteo G. Levisetti, Anish Suri, Ilan Vidavsky, Michael L. Gross, Osami Kanagawa, Emil R. Unanue

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 β-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 β cells, and identified the target as a retroviral envelope glycoprotein expressed on pancreatic β 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 β cell retroviral envelope protein is a target antigen that is selected by the NOD mouse immune system early in the pathogenesis of autoimmune diabetes.

Original languageEnglish
Pages (from-to)1473-1483
Number of pages11
JournalInternational Immunology
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2003

Keywords

  • Autoimmunity
  • Diabetes mellitus
  • Ig
  • Islets of langerhans
  • T lymphocyte

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