Thyrotropin receptor-DNA vaccination of transgenic mice expressing HLA-DR3 or HLA-DQ6b.
Thyrotropin receptor-DNA vaccination of transgenic mice expressing HLA-DR3 or HLA-DQ6b.
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对表达 HLA-DR3 或 HLA-DQ6b 的转基因小鼠进行促甲状腺素受体 DNA 疫苗接种。
DOI：
10.1089/105072503322511300
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
McLachlan,SandraM
中科院分区：
文献类型：
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作者：
Pichurin,Pavel;Chen,Chun-Rong;Pichurina,Oxana;David,Chella;Rapoport,Basil;McLachlan,SandraM
高加索人的Graves病与主要组织相容性（MHC）抗原HLA-DR 3相关。研究易感基因作用的一种方法是使用缺乏鼠MHC的小鼠 而是表达人类HLA抗原。虽然Graves病在动物中不会自发发生，但通过以免疫抑制剂的形式接种促甲状腺激素受体（TSHR）DNA，可以在小鼠中诱导TSHR抗体。 质粒在本研究中，我们的特点TSHR抗体和甲状腺炎的HLA-DR 3转基因小鼠接种TSHR-DNA的发展。作为对照，我们使用HLA-DQ 6 b转基因小鼠， 很少与Graves病相关的抗原。我们观察到，大约30%的DR 3-，但没有DQ 6 b转基因小鼠，开发TSHR抗体可检测的酶联免疫吸附试验（ELISA）。 富含半胱氨酸的氨基末端肽是DR 3小鼠中的主要线性抗体表位，与用TSHR-DNA接种的其他品系一样。部分接种DR 3小鼠的血清在流式细胞术上呈阳性 使用表达TSHR的完整细胞，证明了细胞表面上天然TSHR的识别。尽管这些小鼠都没有甲状腺刺激抗体或甲状腺功能亢进， 甲状腺淋巴细胞浸润。这些数据，连同其他小鼠品系的信息，证明MHC（人和鼠）和非MHC基因有助于TSHR-DNA疫苗接种的结果 表明DR 3转基因小鼠在研究TSHR免疫应答方面具有潜在价值。
Graves' disease in Caucasians is associated with the major histocompatibility (MHC) antigen HLA-DR3. One approach to studying the role of susceptibility genes involves the use of mice that lack murine MHC and instead express human HLA antigens. Although Graves' disease does not arise spontaneously in animals, thyrotropin receptor (TSHR) antibodies can be induced in mice by vaccination with TSHR-DNA in a plasmid. In the present study, we characterized TSHR antibodies and thyroiditis developing in HLA-DR3 transgenic mice vaccinated with TSHR-DNA. As controls, we used mice transgenic for HLA-DQ6b, an MHC antigen rarely associated with Graves' disease. We observed that approximately 30% of DR3-, but none of DQ6b-transgenic mice, developed TSHR antibodies detectable by enzyme-linked immunosorbent assay (ELISA). The cysteine-rich amino terminal peptide was the dominant linear antibody epitope in DR3 mice, as in other strains vaccinated with TSHR-DNA. Sera from some vaccinated DR3 mice were positive on flow cytometry using intact cells expressing the TSHR, demonstrating recognition of the native TSHR on the cell surface. Although none of the these mice had thyroid stimulating antibodies or were hyperthyroid, a few developed lymphocytic infiltration of the thyroid. These data, together with information for other mouse strains, demonstrate that MHC (human and murine) and non-MHC genes contribute to the outcome of TSHR-DNA vaccination and indicate the potential value of DR3 transgenic mice for dissecting immune responses to the TSHR.