Iodination of human thyroglobulin (Tg) alters its immunoreactivity. I. Iodination alters multiple epitopes of human Tg.
Iodination of human thyroglobulin (Tg) alters its immunoreactivity. I. Iodination alters multiple epitopes of human Tg.
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人甲状腺球蛋白 (Tg) 的碘化会改变其免疫反应性。
DOI：
10.1046/j.1365-2249.1998.00643.x
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发表时间：
1998
影响因子：
4.6
通讯作者：
Burek,CL
中科院分区：
文献类型：
--
作者：
Saboori,AM;Rose,NR;Bresler,HS;Vladut-Talor,M;Burek,CL
人三碘甲状腺原氨酸(TG)是自身免疫性甲状腺炎的主要自身抗原之一，是甲状腺激素(T4)和三碘甲状腺原氨酸(T3)合成的场所。甘油三酯的碘化程度可能通过改变其相对于抗体结合的抗原性而对其免疫学性质产生重大影响。我们之前已经制备了一组与TG分子的不同表位结合的MoAbs。在本研究中，我们发现，碘化作用改变了TG分子的构象，不同的MoAb识别它的方式是不同的。单抗137c1识别甘油三酯，而不考虑其碘含量。仅当甘油三酯在体外或体内被碘标记时，单抗42C3才能识别甘油三酯。单抗133B1可识别活体碘标记的甘油三酯和非碘标记的甘油三酯，但该单抗在体外碘标记后不识别甘油三酯。单抗41A5可识别正常(体内)碘化甘油三酯和非碘化甘油三酯的完整甘油三酯和胰多肽，但不结合人工(体外)碘化甘油三酯的胰多肽。根据这些实验结果，我们得出结论，无论是活体方法还是体外法，Tg的碘化都会改变其构象，使一些天然表位“丢失”，而产生一些“新的”表位。新表位的产生在导致自身免疫性疾病的自身免疫反应的产生中可能是重要的。
Human Tg, the site of synthesis of thyroid hormones, thyroxine (T4) and triiodothyronine (T3), is one of the major autoantigens in autoimmune thyroiditis. The degree of iodination of Tg may have a major impact on its immunological properties by changing its antigenicity with respect to antibody binding. We have previously prepared a panel of MoAbs that bind to different epitopes of the Tg molecule. In the present study, we show that iodination alters the conformation of Tg molecule in such a way that it is recognized differently by different MoAbs. Monoclonal antibody 137C1 recognizes Tg regardless of its iodine content. Monoclonal antibody 42C3 recognizes Tg only if the Tg is iodinated eitherin vitroorin vivo. Monoclonal antibody 133B1 recognizes bothin vivoiodinated Tg and non‐iodinated Tg, but this MoAb did not recognize Tg followingin vitroiodination. Monoclonal antibody 41A5 recognizes intact Tg and tryptic peptides of normal (in vivo) iodinated and non‐iodinated Tg, but did not bind the tryptic peptides of artificially (in vitro) iodinated Tg. From the results of these experiments, we conclude that iodination of Tg by eitherin vivoorin vitromethods changes its conformation in such a way that some natural epitopes are ‘lost’ and some ‘new’ epitopes are generated. The generation of new epitopes may be important in the generation of autoimmune responses leading to autoimmune disease.