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

源自自身免疫性甲状腺炎病变的 T 细胞克隆对甲状腺自身抗原的识别；

• 批准号: 05670408
• 负责人: SUGIHARA Shigetaka
• 金额: $ 1.34万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670408/
• 关键词: autoimmune thyroiditis; CD4^+T cell clones; autoantigen; thyroglobulin (Tg); epitope

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.

我们通过使用源自小鼠自身免疫性甲状腺炎病变的 4 种类型的 CD4^+T 细胞克隆，分析了对于诱导自身免疫性甲状腺炎至关重要的甲状腺球蛋白 (Tg) 的抗原决定簇（表位）。 F1 独特的 MHC (H-2^<b/k>) 限制性 T 细胞克隆 N5P-0E14 (TCRVbeta8.3) 对小鼠 Tg 有反应，但对牛和人 Tg 没有反应。 I-A^b 限制性 N5P-0E15 (Vbeta2) 识别小鼠和牛 Tg，但不识别人 Tg。另一方面，I-A^k 限制性 N5P-3B2 (Vbeta14) 和 N6G-4B1 (Vbeta 未知) 可以对所有小鼠、牛和人 Tg 做出反应。这些结果表明Tg分子中至少应该存在3个被T细胞识别的表位。接下来，包括激素酪氨酸在内的 3 种人类 Tg 合成肽；分析了TA (HTg1-11)、TB (HTg2546-2571)和TC (HTg2738-2748)。 TA和TB的氨基酸序列被认为在人类、牛和大鼠Tg中高度保守。相比之下，TC与大鼠Tg的同源性相对较低。此外，TB含有与罗斯巴德算法兼容的氨基酸序列(D-Y-A-S)。这3种合成肽和TB-I(碘化TB)均不能被4种类型的CD4^+T细胞克隆识别。换句话说，诱导CD4+T细胞克隆的自身免疫性甲状腺炎不识别Tg的激素部分。需要使用 cDNA 合成的大肽进行进一步分析，以确定 T 细胞的 Tg 表位。