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

摘要/Abstract

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TCR α、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。

Abstract: Objective To analyze the drift of T cell receptor (TCR) Vα 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 α 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 Vα and Vβ 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 Vα and Vβ families showed an anomalous and oligoclonal expansion. Different
CDR3 sequences of the Vα and Vβ gene family TCR were found in the monoclonal T cells stimulated with BHL-1. Conclusion
CDR3 spectratype drift occurs in TCR α and β chains of T cells after stimulation with human ovarian carcinoma cells and
BHL-1, indicating that the predominant usage of TCR Vα and Vβ families is associated with the specific T cell immune
response mediated by BHL-1.

罗微，温茜，周明乾，马骊. 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[J]. 南方医科大学学报, 2012, 32(07): 919-.

LUO Wei, WEN Qian, ZHOU Mingqian, MA Li. An anti-human ovarian carcinoma and CD3 bispecific single-chain antibody mediates CDR3 spectratype drift of T cell receptor alpha and beta chains[J]. Journal of Southern Medical University, 2012, 32(07): 919-.

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