Non-obese Diabetic Mice Hemizygous at the T Cell Receptor Alpha Locus Are 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 gene are incapable of generating T cells carrying two cell surface TCR alpha chains. Our early results suggested that either dual TCR alpha T cells play a role in insulin-dependent diabetes mellitus (IDDM) induction in NOD mice or that a locus co-segregating with the disrupted TCR alpha locus protected mice from diabetes induction. From the analysis both of mice in which the region co-segregating with the disrupted TCR alpha locus is minimized and of the F1 offspring of NOD mice with the 129 strain (TCR alpha hemizygous mice), the apparent protective effect of the absence of dual TCR alpha T cells is lost; thus, such cells do not appear to play a critical role in autoimmune disease in NOD mice.