T cell receptor restriction of diabetogenic autoimmune NOD T cells

T cell receptor restriction of diabetogenic autoimmune NOD T cells

Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO 80262

Abstract

Restricted use of T cell receptor (TCR) gene segments is characteristic of several induced autoimmune disease models. TCR sequences have previously been unavailable for pathogenic T cells which react with a defined autoantigen in a spontaneous autoimmune disease. The majority of T cell clones, derived from islets of NOD mice which spontaneously develop type I diabetes, react with insulin peptide B-(9–23). We have sequenced the α and β chains of TCRs from these B-(9–23)-reactive T cell clones. No TCR β chain restriction was found. In contrast, the clones (10 of 13) used Vα13 coupled with one of two homologous Jα segments (Jα45 or Jα34 in 8 of 13 clones). Furthermore, 9 of 10 of the Vα13 segments are a novel NOD sequence that we have tentatively termed Vα13.3. This dramatic α chain restriction, similar to the β chain restriction of other autoimmune models, provides a target for diagnostics and immunomodulatory therapy.

Footnotes

↵ * To whom reprint requests should be addressed at: Barbara Davis Center for Childhood Diabetes, 4200 East 9th Avenue, Box B140, Denver, CO 80262.
David W. Talmage, University of Colorado Health Sciences Center, Denver, CO
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. U89719–U89742U89719 U89720 U89721 U89722 U89723 U89724 U89725 U89726 U89727 U89728 U89729 U89730 U89731 U89732 U89733 U89734 U89735 U89736 U89737 U89738 U89739 U89740 U89741 U89742).
ABBREVIATION:

TCR,

T cell receptor