NONOBESE DIABETIC MICE HEMIZYGOTIC AT THE T-CELL RECEPTOR-ALPHA LOCUSARE SUSCEPTIBLE TO DIABETES AND SIALITIS

To test the hypothesis that T cells carrying two T cell receptor (TCR) alpha chains play a role in autoimmunity, we backcrossed the non-obese diabetic (NOD) strain with one carrying a TCR alpha gene disrupted by homologous recombination. Mice carrying one copy of the disrupted gen e are incapable of generating T cells carrying two cell surface TCR al pha chains. Our early results suggested that either dual TCR alpha T c ells play a role in insulin-dependent diabetes mellitus (IDDM) inducti on in NOD mice or that a locus co-segregating with the disrupted TCR a lpha locus protected mice from diabetes induction. From the analysis b oth of mice in which the region co-segregating with the disrupted TCR alpha locus is minimized and of the F-1 offspring of NOD mice with the 129 strain (TCR alpha hemizygous mice), the apparent protective effec t of the absence of dual TCR alpha T cells is lost; thus, such cells d o not appear to play a critical role in autoimmune disease in NOD mice .