沙眼衣原体（Chlamydia trachomatis，CT）是一种革兰氏阴性、专性细胞内寄生菌，可感染尿道、阴道与鼻咽等黏膜上皮细胞以及眼结膜等处，引起沙眼、尿道炎、宫颈炎、新生儿结膜炎等疾病。其中，L2型CT可引起性病淋巴肉芽肿，其侵袭力较其他血清型强，需要长疗程治疗，受到广泛关注。研究表明，细胞表面促红细胞生成素产生肝细胞受体A2（Erythropoietin-Producing Hepatocellular Receptor A2，EphA2）可介导L2型CT粘附和侵袭，干扰二者相互作用可显著降低L2型CT的感染。本研究通过对L2型CT感染的人宫颈上皮细胞进行生物信息学分析，发现EphA2在感染组中表达显著上调。本研究成功构建并表达纯化了靶向EphA2的双价抗体EphA2-scFv-Fc。通过ELISA实验证实，EphA2-scFv-Fc与L2型CT易感细胞HUVEC表面的EphA2受体之间存在剂量依赖性的特异性结合。本研究不仅揭示了EphA2作为CT感染过程中的关键作用，还成功开发了可特异性靶向EphA2的双价抗体，为L2型CT感染的治疗提供了重要的基础。
Abstract
Chlamydia trachomatis (CT) is a Gram-negative, obligate intracellular parasite that can infect mucosal epithelial cells such as the urethra, vagina, and nasopharynx, as well as the conjunctiva, causing diseases such as trachoma, urethritis, cervicitis, and neonatal conjunctivitis. Among them, L2 CT can cause sexually transmitted lymphogranuloma, which is more invasive than other serotypes and requires long-term treatment, receiving widespread attention. Research has shown that the production of erythropoietin producing hepatocyte receptor A2 (EphA2) on the cell surface can mediate the adhesion and invasion of CT L2, and interfering with their interaction can significantly reduce the infection of CT L2. This study conducted bioinformatics analysis on human cervical epithelial cells infected with CT L2 and found that EphA2 expression was significantly upregulated in the infected group. This study successfully constructed, expressed, and purified a bivalent antibody targeting EphA2, named as EphA2-scFv-Fc. Through ELISA experiments, it was confirmed that there is a dose-dependent specific binding between EphA2-scFv-Fc and EphA2 receptors on the surface of CT L2 susceptible cells HUVEC. This study not only revealed the crucial role of EphA2 in the process of CT infection, but also successfully developed bivalent antibodies that can specifically target EphA2, providing an important foundation for the treatment of CT L2 infection.
关键词
沙眼衣原体 /
促红细胞生成素产生的肝细胞受体A2 /
双价抗体
Key words
Chlamydia trachomatis /
Erythropoietin Producing Hepatocyte Receptor A2 /
Bivalent Antibody
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