抗人卵巢癌/抗人CD3单链双特异性抗体介导的αβT细胞CDR3谱系漂移  

An anti-human ovarian carcinoma and CD3 bispecific single-chain antibody mediates CDR3 spectratype drift of T cell receptor alpha and beta chains

作　　者：罗微[1] 温茜[1] 周明乾[1] 马骊[1] 

机构地区：[1]南方医科大学生物技术学院分子免疫学研究所,广东广州510515

出　　处：《南方医科大学学报》2012年第7期919-923,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(81171539;30972680);广东省自然科学基金重点项目(S2011020003154);高等学校博士学科点专项科研基金(20114433110002)~~

摘　　要：目的探讨抗人卵巢癌/抗人CD3单链双特异性抗体(BHL-1)介导的αβT细胞CDR3谱系漂移,为双特异性抗体介导的T细胞免疫应答机制提供理论基础。方法采用免疫扫描谱型分析技术,分析6例正常献血员T细胞在人卵巢癌SKOV3细胞联合BHL-1刺激前后的TCR库多样性变化(CDR3谱型分布特征)及刺激后T细胞TCRα、β链CDR3优势利用情况,对克隆性增生T细胞的CDR3区进行序列分析。结果刺激前6例正常献血员TCR CDR3谱型均呈高斯分布,刺激后发生CDR3谱系漂移,部分TCR Vα、Vβ家族出现优势增生,明确了BHL-1介导下单克隆增生T细胞的α、β链CDR3序列。结论 SKOV3联合BHL-1诱导的T细胞CDR3谱系出现明显漂移,提示CDR3的选择性表达可能与BHL-1介导的特异性T细胞免疫反应有关,特异应答T细胞TCR CDR3序列的确定,将为卵巢癌的T细胞免疫治疗提供基础。Objective To analyze the drift of T cell receptor （TCR） Va and Vβ gene family CDR3 spectratype in response to ovarian carcinoma cells mediated by an anti-human ovarian carcinoma/CD3 bispecific single-chain antibody （BHL-1）, and explore the mechanism of the bispecific single-chain antibody-mediated T cell immune response. Methods Immunoscopic spectratyping technique was used to analyze the TCR repertoire diversity （CDR3 spectratype distribution） of the T cells from 6 healthy donors before and after stimulation of the cells with human ovarian carcinoma in the presence of BHL-1. The predominant usage of TCR a and β chain CDR3 was analyzed after the stimulation, and sequence analysis was performed for the CDR3 region of the monoclonal T cells. Results The spectratypes of Va and Va gene family TCR CDR3 region showed a Gaussian distribution before stimulation of the T cells from the 6 donors. After stimulation of the T cells, CDR3 spectratype drift occurred in the T cells, and some TCR Va and Vβ families showed an anomalous and oligoclonal expansion. Different CDR3 sequences of the Va and Vβ gene family TCR were found in the monoclonal T cells stimulated with BHL-1. Conclusion CDR3 spectratype drift occurs in TCR a and β chains of T cells after stimulation with human ovarian carcinoma cells and BHL-1, indicating that the predominant usage of TCR Va and Vβ families is associated with the specific T cell immune response mediated by BHL-1.

关 键 词：双特异性抗体 抗人卵巢癌/抗人CD3单链双特异性抗体 T细胞受体 互补决定区3 基因扫描 

分 类 号：R392[医药卫生—免疫学]