DISTINCT DELTA-T-CELL RECEPTOR REPERTOIRES IN MONOZYGOTIC TWINS CONCORDANT FOR CELIAC-DISEASE

One of the hallmarks of coeliac disease, both active and treated, is a n increased number and proportion of gamma/delta intraepithelial T lym phocytes in the small intestinal mucosa, and an increased number of ga mma/delta T cells in the small intestinal mucosa of coeliac disease pa tients has been associated with the inheritance of specific HLA class II DQ alleles. Nonetheless, the contribution of genetic factors to the development of the T cell receptor (TCR) delta repertoire in coeliac disease is not known. We have assessed the contribution of genetic fac tors to development of the TCR delta repertoire in coeliac disease, by characterizing the junctional diversity of TCR delta transcripts expr essed in the intestine and peripheral blood of a pair of monozygotic ( MZ) twins concordant for coeliac disease. TCR V delta 1, V delta 2 and V delta 3 transcripts from small intestinal and colon biopsies, and f rom peripheral blood mononuclear cells, were amplified by polymerase c hain reaction (PCR) and the complementarity determining region (CDR)3 domains of TCR delta transcripts were analysed by denaturing PAGE and direct nucleotide sequencing. The repertoire of TCR delta transcripts and CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins concordant for coeliac disease exhibited no overlap. The TCR de lta repertoire in each twin was oligoclonal, and complexity of the jun ctional regions of their TCR delta transcripts was typical of the repe rtoire in healthy adults. Thus, genetically identical individuals with coeliac disease have distinct, non-overlapping TCR delta repertoires. Moreover, genetic factors that determine disease susceptibility do no t appear to select for specific TCR delta sequences or CDR3 amino acid motifs.