Thyroglobulin peptides of specific primary hormonogenic sites can generate cytotoxic T cells and serve as target autoantigens in experimental autoimmune thyroiditis.
Thyroglobulin peptides of specific primary hormonogenic sites can generate cytotoxic T cells and serve as target autoantigens in experimental autoimmune thyroiditis.
复制标题
DOI：
10.1006/clin.1997.4487
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Q. Wan;D. Mccormick;C. David;Y. Kong
中科院分区：
文献类型：
--
作者：
Q. Wan;D. Mccormick;C. David;Y. Kong
先前我们已经证明，人(H)甲状腺球蛋白(TG)5(1-12)和2553(2549-2560)位含有甲状腺激素(T4)的12聚体多肽以及甲状腺原氨酸(T0)取代的2553多肽能够激活T细胞，使T细胞渗入甲状腺(促甲状腺激素)。相反，多肽T4(2567)和T0(2567)(2559-2570)则不是。为了确定T4(5)、T4(2553)和T0(2553)是否能激活细胞毒性T细胞(TC)，并将它们负载到指示细胞(BW5147淋巴瘤，H2k)上，用MTG、HTG或TG肽免疫CBA小鼠的淋巴结细胞进行体外培养。在MTG或HTG激活后，在效应器：靶细胞比为50：1的18h，51Cr释放实验中检测到MTG和HTG负载的靶细胞的TC。这些TC也可以杀死标记有T4(5)、T4(2553)或T0(2553)的靶细胞，但不能杀死对照多肽T4(2567)。当MTG刺激的淋巴细胞与T4(5)、T4(2553)或T0(2553)共同培养时，也能产生针对相应多肽标记的靶细胞的特异性TC。这些数据提示，这些多肽的促甲状腺功能之一与甲状腺球蛋白的生成有关。此外，这些保守的Tg自身表位也是Tc的靶抗原。
Previously we demonstrated that thyroxine (T4)-containing, 12-mer peptides from positions 5 (1-12) and 2553 (2549-2560), as well as thyronine (T0)-substituted 2553 peptide, derived from human (H) thyroglobulin (Tg) are capable of activating T cells that infiltrate the thyroid (thyroiditogenic). In contrast, peptides T4(2567) and T0(2567) (2559-2570) are not. To determine if these thyroiditogenic peptides, T4(5), T4(2553), and T0(2553), activated cytotoxic T cells (Tc) and served as target autoantigens when loaded onto indicator cells (BW5147 lymphoma, H2k), lymph node cells from CBA mice immunized with mouse (M) Tg were cultured in vitro with MTg, HTg, or Tg peptide. After MTg or HTg activation, Tc were detected for both MTg- and HTg-loaded target cells in an 18-h, 51Cr-release assay at an effector:target cell ratio of 50:1. These Tc also killed target cells labeled with T4(5), T4(2553), or T0(2553), but not the control peptide T4(2567). When MTg-primed lymphocytes were cultured with T4(5), T4(2553), or T0(2553), specific Tc were also generated against target cells labeled with the respective peptide. The data suggest that one of the thyroiditogenic properties of these peptides previously shown by adoptive transfer of thyroiditis is related to the generation of Tc. In addition, these conserved autoepitopes of Tg also serve as target antigens for Tc.