IDENTIFICATION OF A LIMITED T-CELL RECEPTOR-BETA-CHAIN VARIABLE REGION REPERTOIRE ASSOCIATED WITH DIABETES IN THE BB-RAT

Diabetes-prone BB rats spontaneously develop type 1 diabetes due to a T-cell-dependent destruction of insulin-producing beta-islet cells. A number of T-cell abnormalities including lymphopenia, poor cell-mediated responsiveness to alloantigen, and an absence of an RT6+ T-cell subset are associated with disease susceptibility. Our previous studies have implicated the thymic antigen-presenting cell in influencing disease potential and responsiveness to alloantigen. Since this cell type is also known to influence T-cell receptor expression in developing thymocytes, we examined the thymic and peripheral T-cell receptor beta-chain variable region repertoire in diabetes-prone and diabetes-resistant rats. Our findings indicate that animals susceptible to diabetes induction have a characteristic and limited peripheral beta-chain variable region repertoire that differs markedly from that expressed in the thymus.