T-cell antigen receptor alpha chain polymorphisms in insulin-dependent diabetes

Abstract

Insulin-dependent diabetes is a chronic autoimmune disease probably mediated by T cells. We examined the alpha chain of the T-cell antigen receptor in two models of this illness (man and BB rat) to determine any association with autoimmune diabetes. We conducted a population study in man, using a human alpha chain probe, pGA-5, and restriction enzyme Bgl 11. Two allelic forms and three RFLP patterns, 2.8 and 3.0 kb homozygous and 2.8 3.0 heterozygous, were detected. There was no difference in the frequency of these RFLPs among the 50 Type I diabetic patients and 48 controls tested. BB rats develop a spontaneous T-cell mediated autoimmune diabetes. The diabetes has been linked in several breeding studies to an undetermined autosomal recessive gene causing T-cell lymphopenia. We were able to differentiate the T-cell antigen receptor alpha chain of the diabetic BB and control BBN rats using the restriction enzyme EcoR1 and a murine alpha chain probe, TT11. The BB rat had a haplotype characterized by the presence of 4.7 and 5.8 kb bands, and the absence of 1.4, 2.2, 2.6, 3.6, 3.9, 4.1, and 6.1 kb bands. In a breeding study with BB and BBN rats, diabetic animals of the F2 generation demonstrated no linkage with the BBs' alpha chain, nor was lymphopenia linked to the alpha chain of the BB rat. These results suggest that autoimmune diabetes is not linked to the T-cell antigen receptor alpha chain in the BB rat, nor is it associated with alpha chain constant region polymorphisms in Type I diabetes in man.