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一种抗人卵巢癌和CD3双特异性单链抗体介导T细胞受体α和β链的CDR3谱型漂移

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

作者信息

Luo Wei, Wen Qian, Zhou Mingqian, Ma Li

机构信息

Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2012 Jun;32(7):919-23.

PMID:22820567
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 Vβ 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 Vβ 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.

摘要

目的

分析抗人卵巢癌/CD3双特异性单链抗体(BHL-1)介导的T细胞受体(TCR)Vα和Vβ基因家族CDR3谱型在卵巢癌细胞作用下的漂移情况,探讨双特异性单链抗体介导的T细胞免疫应答机制。

方法

采用免疫谱型分析技术,分析6名健康供者的T细胞在BHL-1存在下经人卵巢癌细胞刺激前后的TCR库多样性(CDR3谱型分布)。刺激后分析TCR α和Vβ链CDR3的优势使用情况,并对单克隆T细胞的CDR3区域进行序列分析。

结果

6名供者的T细胞刺激前,Vα和Vβ基因家族TCR CDR3区域的谱型呈高斯分布。T细胞刺激后,T细胞中发生了CDR3谱型漂移,部分TCR Vα和Vβ家族出现异常和寡克隆扩增。在BHL-1刺激的单克隆T细胞中发现了Vα和Vβ基因家族TCR的不同CDR3序列。

结论

人卵巢癌细胞和BHL-1刺激后,T细胞的TCR α和Vβ链发生CDR3谱型漂移,表明TCR Vα和Vβ家族的优势使用与BHL-1介导的特异性T细胞免疫应答有关。

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