W. Holtmeier et al., DISTINCT DELTA-T-CELL RECEPTOR REPERTOIRES IN MONOZYGOTIC TWINS CONCORDANT FOR CELIAC-DISEASE, Clinical and experimental immunology, 107(1), 1997, pp. 148-157
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.