Antigenic determinants of thyroglobulin relating to mouse experimental autoimmune thyroiditis

为了阐明小鼠自身免疫性甲状腺炎（autoimmune thyroiditis，AAT）中对甲状腺球蛋白（thyroglobulin，Tg）的自身免疫反应的特异性，我们研究了良好和不良应答小鼠对Tg的抗原特异性增殖反应以及Tg或Tg片段免疫诱导的实验性自身免疫性甲状腺炎（experimental autoimmune thyroiditis，EAT）。用葡萄球菌V8蛋白酶消化小鼠和人的Tg，用高效液相色谱法将其分离成8个小鼠Tg组分（Fr 1-Fr 8：470 kDa-8 kDa）和7个人Tg组分（Fr 1-Fr 7：470 kDa-14 kDa）。主要研究结果如下：1. CBA小鼠的淋巴细胞增殖的Tg和Tg Fr，当小鼠用小鼠Tg免疫。与此相反，B10或BALB/c淋巴细胞引发小鼠Tg没有增殖可检测到的小鼠Tg，但在一些小鼠Tg Fr的反应增殖。此外，当BALB/c小鼠免疫小鼠Tg Fr 4，而不是Tg，增殖反应小鼠Tg以及Tg Fr在这些小鼠中开发。这些数据表明，能够响应Tg的T细胞存在于BALB/c小鼠中，尽管它们是对Tg的低应答品系。低应答小鼠对Tg的免疫应答可能受到调节细胞的抑制.小鼠Tg Fr 1-Fr 5（470 kDa-35 kDa）免疫B6 C3 F1小鼠可诱导EAT，而分子量小于18 kDa的小鼠Tg Fr免疫B6 C3 F1小鼠几乎不诱导EAT。人Tg Fr 1-Fr 6（470 kDa-18 kDa）免疫B6 C3 F1小鼠，也可诱导EAT。此外，用牛Tg、人Tg以及小鼠Tg免疫小鼠诱发甲状腺炎。这些研究结果表明，限制性的Tg抗原决定簇，包括种间交叉反应的Tg抗原决定簇，与甲状腺炎。

To elucidate the specificities of autoimmune response to thyroglobulin (Tg) in murine autoimmune thyroiditis, we studied antigen specific proliferative response to Tg in good and poor responder mice and experimental autoimmune thyroiditis (EAT) induced by immunization with Tg or Tg fragments. Mouse and human Tg digested with staphylococcal V8 protease were separated into 8 mouse Tg fractions (Frl-Fr8 : 470kDa-8kDa) and 7 human Tg fractions (Frl-Fr7 : 470kDa-14kDa) by high performance liquid chromatography. The results obtained are as follows :1. Lymphocytes from CBA mice proliferated in response to both Tg and Tg Fr, when mice were immunized with mouse Tg. In contrast, B10 or BALB/c lymphocytes primed with mouse Tg did not proliferate detectably in response to mouse Tg but proliferated in response to some mouse Tg Fr. In addition, when BALB/c mice were immunized with mouse Tg Fr 4 instead of Tg, proliferative response to mouse Tg as well as Tg Fr developed in these mice. These data indicate that T cells capable of responding to Tg exist in BALB/c mice, although they are low responder strain to Tg. Immune response to Tg in low responder mice might be suppressed by regulatory cells.2. EAT was induced by immunization with mouse Tg Fr1-Fr5 (470kDa-35kDa) in B6C3F1 mice, whereas EAT was hardly induced by immunization with mouse Tg Fr with molecular weight smaller than 18kDa. When B6C3F1 mice were immunized with human Tg Fr1-Fr6 (470kDa-18kDa), EAT was also induced in them. In addition, immunization, immunization with bovine Tg, human Tg as well as mouse Tg induced thyroiditis in mice. These findings suggest that restricted antigenic determinants of Tg, including interspecies cross-reactive Tg antigenic determinants, are related to thyroiditis.