The role of T cells expressing TcR V beta 13 in autoimmune thyroiditis induced by transfer of mouse thyroglobulin-activated lymphocytes: identification of two common CDR3 motifs.

The transfer of lymphocytes from mouse thyroglobulin (mTg)-immunized CBA/J (H-2k) mice following in vitro activation with mTg initiates experimental autoimmune thyroiditis (EAT) in syngeneic recipients. We have analyzed the T cell receptor (TcR) V gene families used by the intrathyroidal lymphocytic infiltrate of such mice. Using a radiolabeled RT-PCR technique with oligonucleotides detecting 17 mouse TcR V beta gene 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 with two clonally expanded T cell populations. Sequencing of the homogeneous RT-PCR products from these V beta 13++ populations confirmed the presence of clonal expanded T cells and identified two recurrent CDR3 motifs LTGKDTQ and LGEQ present in six of the seven samples. Both these motifs had been found as contributors to the T cell population in our previous studies of CBA/J mouse thyroiditis induced by active immunization with heterologous human (h) Tg. These data suggest that the autoepitope recognized was shared between hTg and mTg. It appears, therefore, that in transfer thyroiditis the intrathyroidal T cell clonal proliferation 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 utilize two distinct CDR3 motifs. CDR3 size heterogeneity in many of the 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 the development of autoimmune thyroiditis.