Antigenic determinants of thyroglobulin relating to mouse experimental autoimmune thyroiditis

为了阐明自身免疫性甲状腺炎小鼠对甲状腺球蛋白(TG)的自身免疫应答的特异性，我们研究了免疫应答良好和应答差的小鼠以及用TG或TG片段免疫诱导的实验性自身免疫性甲状腺炎(EAT)中对TG的抗原特异性增殖反应。用高效液相色谱法将葡萄球菌V8酶消化的小鼠和人TG分别分离为8个小鼠TG组分(Fr1-Fr8：470 kDa-8 kDa)和7个人TG组分(Fr1-Fr7：470 kDa-14 kDa)。结果如下：1.小鼠TG免疫后，CBA小鼠淋巴细胞在TG和TG Fr刺激下均有增殖反应。相反，用小鼠Tg诱导的B10或BALB/c淋巴细胞对小鼠Tg没有明显的增殖反应，但对某些小鼠Tg Fr有明显的增殖反应。此外，用小鼠TG Fr 4免疫BALB/c小鼠后，小鼠对小鼠TG和Tg Fr均产生增殖反应。这些数据表明，BALB/c小鼠体内存在对甘油三酯有应答能力的T细胞，尽管它们对甘油三酯的反应性较低。结论：1.低应答小鼠对甘油三酯的免疫应答可能受到调节细胞的抑制。小鼠TG Fr1-Fr5(470 kDa-35 kDa)免疫B6C3F1小鼠可诱导EAT，而相对分子质量小于18 kDa的小鼠TG Fr几乎不能诱导EAT。用人TG Fr1-FR6(470 kDa-18 kDa)免疫B6C3F1小鼠，也能诱导EAT。此外，免疫、免疫牛TG、人TG以及小鼠TG均可引起小鼠甲状腺炎。这些发现表明，甘油三酯的限制性抗原决定簇，包括种间交叉反应的甘油三酯抗原决定簇，与甲状腺炎有关。

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.