Recognition of thyroid autoantigen by T cell clones derived from autoimmune thyroiditis lesions ; Analysis of epitope in thyroglobulin

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We analyzed the antigenic determinants (epitopes) of thyroglobulin (Tg) critical for the induction of autoimmune thyroiditis by using 4 types of CD4^+T cell clones derived from autoimmune thyroiditis lesions in mice. F1 unique MHC (H-2^<b/k>) restricted T cell clone, N5P-0E14 (TCRVbeta8.3) responded to mouse Tg but not to bovine and human Tg. I-A^b restricted, N5P-0E15 (Vbeta2) recognized mouse and boving Tg but not human Tg. On the other hand, I-A^k restricted, N5P-3B2 (Vbeta14) and N6G-4B1 (Vbetaunknown) could respond to all of mouse, bovine and human Tg. These results seggest that at least 3 epitopes recognized by T cells should exist in Tg molecule. Next, 3 synthetic peptides of human Tg including hormonogenic tyrosine ; TA (HTg1-11) , TB (HTg2546-2571) and TC (HTg2738-2748) , were analyzed. Amino acid sequence of TA and TB were considered highly conserved among human, boving and rat Tg. In contrast, homology of TC to rat Tg was relatively low. In addition, TB contained amino acid sequence (D-Y-A-S) which is compatible to Rothbard's algorithm. None of these 3 synthetic peptides and TB-I (iodinated TB) could not be recognized by 4 types of CD4^+T cell clones. In other words, autoimmune thyroiditis inducing CD4^+T cell clones did not recognize hormonogenic portion of Tg. Further analysis using large peptide synthesized by cDNA will be required to identify epitopes of Tg for T cells.