Generation and Characterization of Four Novel Monoclonal Antibodies Against Human Programmed Death-1 Molecule
Generation and Characterization of Four Novel Monoclonal Antibodies Against Human Programmed Death-1 Molecule
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四种新型抗人程序性死亡 1 分子单克隆抗体的生成和表征
DOI：
10.1089/hyb.2009.0091
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Zhang, Xueguang
中科院分区：
文献类型：
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作者：
Chen, Yongjing;Hu, Zhenhua;Zhang, Xueguang
程序性死亡-1（PD-1，CD 279）是CD 28超家族的一种抑制性共刺激分子，在免疫应答中起着关键作用。本研究采用杂交瘤技术制备了4株新型鼠抗人PD-1单克隆抗体，并对其免疫学特性进行了研究。结果显示，所有MAb（克隆9 H1、4 B 9、8 F5和1F 8）均为IgG 1（κ），并与人PD-1特异性结合。通过相互竞争，我们发现抗体识别PD-1抗原的三个不同表位，并且9 H1 MAb可以阻断PD-1/PD-L1和PD-1/PD-L2相互作用。PD-1与MAb 9 H1的交联显著阻断PD-1负信号并促进T细胞增殖。4 B 9和9 H1单克隆抗体可用于间接ELISA检测。因此，筛选出特异性高、活性不同的抗人PD-1单克隆抗体，为进一步研究该分子奠定了基础。
Programmed death-1 (PD-1, CD279), an inhibitory co-stimulatory molecule of the CD28 superfamily, plays a critical role in immune response. In this report, four novel mouse anti-human PD-1 monoclonal antibodies (MAbs) were prepared using hybridoma technology and immunological characteristics of the MAbs were determined. The results showed that all the MAbs (clones 9H1, 4B9, 8F5, and 1F8) were IgG1(kappa) and bound specifically to human PD-1. By mutual competition, we found that the antibodies recognized three different epitopes of PD-1 antigen and 9H1 MAb could block both PD-1/PD-L1 and PD-1/PD-L2 interaction. Crosslinking of PD-1 with MAb 9H1 markedly blocked PD-1 negative signal and promoted T cell proliferation. In addition, 4B9 and 9H1 MAbs were suitable for indirect ELISA detection. Thus, the MAbs against human PD-1 with high specificity and different activity would be useful for the further study of this molecule.