ANTIGEN RECEPTOR VARIABLE REGION REPERTOIRES EXPRESSED BY T-CELLS INFILTRATING THYROID, RETROORBITAL, AND PRETIBIAL TISSUE IN GRAVES-DISEASE

To date, it has remained unclear whether T cells infiltrating thyroid, retroorbital, and pretibial tissue of patients with Graves' ophthalmo pathy and pretibial dermopathy represent a primary immune response tha t is directed against certain antigenic determinants shared among thes e involved tissues. To characterize these T cells at the molecular lev el, we compared the T cell antigen receptor (TcR) variable (V) region gene usage in thyroid, retroorbital, pretibial tissue, and peripheral blood mononuclear cells of two patients with Graves' disease, ophthalm opathy, and pretibial dermopathy. Ribonucleic acid was extracted, reve rse transcribed, and amplified using the PCR and 22 V alpha and 23 V b eta gene-specific oligonucleotide primers. The resulting TcR V alpha a nd V beta transcripts were verified by Southern hybridization analysis using TcR C region-specific, digoxigenin-labeled oligonucleotide prob es. In addition, complementarity determining regions 3 and junctional regions of TcR V beta genes were sequenced. Marked similarities of int rathyroidal, retroorbital, and pretibial TcR V alpha and V beta gene r epertoires were noted with respect to the degree of TcR V gene restric tion and the patterns of individual V genes expressed. Sequence analys is of junctional domains of V beta families revealed oligoclonality of intrathyroidal, retroorbital, and pretibial T cells. In addition, cer tain conserved junctional motifs were shared by T cells derived the th yroid gland and the extrathyroidal sites. Our results suggest that in the two patients with Graves' disease and extrathyroidal manifestation s studied, similar antigenic determinants may have contributed to the recruitment and oligoclonal expansion of T cells both within the thyro id gland and at the involved extrathyroidal sites.