ANALYSIS OF THE SPONTANEOUS T-CELL RESPONSE TO INSULIN IN NOD MICE

Insulin-specific T cells have been found to be present in high frequen cy among nominally islet-cell-specific T cells in the islet infiltrate s that accumulate in NOD mice. In a previous report in which clones ob tained from 7- and 12-week-old mice were examined, we identified a 15- residue peptide of the B chain as the dominant epitope for this respon se. Despite the fact that the response to insulin appears to be direct ed toward this single peptide, diverse TCR VP usage was observed. That insulin-specific T cells contribute to beta cell damage is suggested by the fact that all clones tested could mediate beta cell destruction upon adoptive transfer. In the present report we extend this examinat ion of insulin-specific T cells to lines and clones established from m ice ranging in age from 4-12 weeks. These clones were found to be very similar to those from 7- and 12-week-old mice. The response was direc ted to the same peptide and most were found to produce IFN gamma, but none produced IL-4.