Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains

S. I. Ymer, D. Huang, G. Penna, S. Gregori, K. Branson, L. Adorini, G. Morahan

Research output: Contribution to journalArticle

Abstract

Interleukin (Il)-12 is a heterodimeric cytokine composed of 35 and 40 kD chains that plays a key role in the induction of Th1 cells, a T cell subset involved in many autoimmune diseases. We report here the cDNA sequence encoding the IL-12 p40 subunit from the autoimmune-prone non-obese diabetic (NOD) mouse, which spontaneously develops type 1 diabetes. Compared with the C57BL/6 sequence, there are two base changes that lead to amino acid replacements. Other autoimmune-prone strains, but not the diabetes-resistant NOR strain, share the same allele as NOD. We found both trans- and cis- allele-dependent effects on levels of basal and induced IL-12p40 expression. Furthermore, we show that one of these changes results in a structural change in the p40 molecule, as evidenced by the failure of a monoclonal antibody to bind NOD IL-12. These findings have implications for the predisposition to autoimmune responses in NOD and other autoimmune-prone mouse strains.

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalGenes and Immunity
Volume3
Issue number3
DOIs
Publication statusPublished - May 2002

Keywords

  • Autoimmunity
  • Epitope
  • Genetic regulation
  • IL 12b
  • Immunogenetics

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

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