THE ROLE OF T-CELLS EXPRESSING TCR V-BETA-13 IN AUTOIMMUNE-THYROIDITIS INDUCED BY TRANSFER OF MOUSE THYROGLOBULIN-ACTIVATED LYMPHOCYTES - IDENTIFICATION OF 2 COMMON CDR3 MOTIFS

The transfer of lymphocytes from mouse thyroglobulin (mTg)-immunized C BA/J (H-2(k)) mice following in vitro activation with mTg initiates ex perimental autoimmune thyroiditis (EAT) in syngeneic recipients. We ha ve analyzed the T cell receptor (TcR) V gene families used by the intr athyroidal lymphocytic infiltrate of such mice. Using a radiolabeled R T-PCR technique with oligonucleotides detecting 17 mouse TcR V beta ge ne families to examine the heterogeneity of the amplified V-D-J (CDR3) fragments, we demonstrated that only the TcR V beta 13 amplifications consistently showed two similar homogeneous CDR3 sizes consistent wit h two clonally expanded T cell populations. Sequencing of the homogeno us RT-PCR products from these V beta 13 populations confirmed the pres ence of clonal expanded T cells and identified two recurrent CDR3 moti fs LTGKDTQ and LGEQ present in six of the seven samples. Both these mo tifs had been found as contributors to the T cell population in our pr evious studies of CBA/J mouse thyroiditis induced by active immunizati on with heterologous human (h) Tg. These data suggest that the autoepi tope recognized was shared between hTg and mTg. It appears, therefore, that in transfer thyroiditis the intrathyroidal T cell clonal prolife ration follows the homing of V beta 13 antigen-specific T cells which have been expanded by a brief (3 day) in vitro activation to mTg and u tilize two distinct CDR3 motifs. CDR3 size heterogeneity in many of th e other expressed V gene families also suggested the accumulation and recruitment of selected bystander T cells responding to additional but limited Tg or other self epitopes, perhaps on the basis of CDR3 shape rather than sequence. Such T cells may also have integral roles in th e development of autoimmune thyroiditis. 1996 Academic Press, Inc.