T-CELL RECEPTOR RESTRICTION OF DIABETOGENIC AUTOIMMUNE NOD T-CELLS

Restricted use of T cell receptor (TCR) gene segments is characteristi c of several induced autoimmune disease models, TCR sequences have pre viously been unavailable for pathogenic T cells which react with a def ined autoantigen in a spontaneous autoimmune disease, The majority of T cell clones, derived from islets of NOD mice which spontaneously dev elop type I diabetes, react with insulin peptide B-(9-23). We have seq uenced the alpha and beta chains of TCRs from these B-(9-23)-reactive T cell clones. No TCR beta chain restriction was found. In contrast, t he clones (10 of 13) used V alpha 13 coupled with one of two homologou s J alpha segments (J alpha 45 or J alpha 34 in 8 of 13 clones). Furth ermore, 9 of 10 of the V alpha 13 segments are a novel NOD sequence th at we have tentatively termed V alpha 13.3. This dramatic alpha chain restriction, similar to the beta chain restriction of other autoimmune models, provides a target for diagnostics and immunomodulatory therap y.