Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease

Abstract

Abstract One of the hallmarks of coeliac disease, both active and treated, is an increased number and proportion of γ/δ intraepithelial T lymphocytes in the small intestinal mucosa, and an increased number of γ/δ T cells in the small intestinal mucosa of coeliac disease patients 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) δ repertoire in coeliac disease is not known. We have assessed the contribution of genetic factors to development of the TCR δ repertoire in coeliac disease, by characterizing the junctional diversity of TCR δ transcripts expressed in the intestine and peripheral blood of a pair of monozygotic (MZ) twins concordant for coeliac disease. TCR Vδ1, Vδ2 and Vδ3 transcripts from small intestinal and colon biopsies, and from peripheral blood mononuclear cells, were amplified by polymerase chain reaction (PCR) and the complementarity determining region (CDR)3 domains of TCR δ transcripts were analysed by denaturing PAGE and direct nucleotide sequencing. The repertoire of TCR δ transcripts and CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins concordant for coeliac disease exhibited no overlap. The TCR δ repertoire in each twin was oligoclonal, and complexity of the junctional regions of their TCR δ transcripts was typical of the repertoire in healthy adults. Thus, genetically identical individuals with coeliac disease have distinct, non-overlapping TCR δ repertoires. Moreover, genetic factors that determine disease susceptibility do not appear to select for specific TCR δ sequences or CDR3 amino acid motifs.