结核病的gamma delta T细胞特异性诊断及其相关配体鉴定研究

项目名称： 结核病的gamma delta T细胞特异性诊断及其相关配体鉴定研究

项目编号： No.81471574

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 何维

作者单位： 中国医学科学院基础医学研究所

项目金额： 75万元

中文摘要： 结核病是一种由结核杆菌引起的全身多系统多器官的疾病，因其感染率，发病率和死亡率很高，给人类的健康带来了巨大的挑战。由于诊断方法所限，严重影响了结核病的及时诊断。γδT细胞处于抗感染免疫的防御一线，能在结核杆菌感染的最早期活化，清除病原体，在机体对抗结核杆菌感染的免疫应答发挥重要作用。本研究拟通过多重PCR和高通量测序的方法，对健康人和结核病患者的γδT细胞CDR3δ序列进行对比分析，找到特异性的结核杆菌感染相关的CDR3δ多态性特征，并选择其中的优势序列，应用实验室前期已建立一种基于CDR3δ肽的结合特异性的筛选方法，鉴定出γδT细胞所识别的相关配体。本研究能够建立一个基于γδT细胞CDR3δ多态性的结核病早期诊断的免疫学方法，鉴定出γδT细胞所识别的相关配体，为深入阐明γδT细胞在抗结核杆菌感染的免疫应答中的作用机制奠定基础。

中文关键词： gamma；delta；T细胞；结核病；诊断；配体

英文摘要： Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which affects almost any tissues or organs of the body. With high prevalence, morbidity and mortality, tuberculosis has brought great challenges to humans. The short of efficient diagnostic methods has seriously affected the timely diagnosis of tuberculosis. γδT cells are implicated in the first line of the immune defense against infection and can be activated at the earliest stage of Mycobacterium tuberculosis infection. γδT cells play an important role in the removal of pathogens and the body's immune response against Mycobacterium tuberculosis infection. In this study, multiplex PCR and high-throughput sequencing will be performed for the analysis of the sequences of CDR3δ of γδT cells from healthy individuals and patients with tuberculosis in order to identify the specific characteristics of CDR3δ polymorphisms associated with Mycobacterium tuberculosis infection. Then we will identify the predominant sequences and the ligands recognized by γδT cells though an established method based on the binding specificity of CDR3δ in our laboratory. This study will establish an immunological method based on CDR3δ polymorphism of γδT cells for early diagnosis of TB and identify the ligands recognized by γδT cells, which lays the foundation for further elucidating the mechanism of γδT cells in the immune response against Mycobacterium tuberculosis infection.

英文关键词： gamma delta T cell;tuberculosis;diagnosis;ligand