Fine epitope mapping of humanized anti-IgE monoclonal antibody omalizumab
Fine epitope mapping of humanized anti-IgE monoclonal antibody omalizumab
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DOI：
10.1016/j.bbrc.2008.08.055
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发表时间：
2008-10-31
影响因子：
3.1
通讯作者：
Guo, Yajun
中科院分区：
文献类型：
--
作者：
Zheng, Lei;Li, Bohua;Guo, Yajun
Omalizumab是一种人源化抗IgE抗体，可抑制IgE与其在肥大细胞和嗜碱性细胞上的受体结合，从而阻断IgE介导的药物介质从这些细胞释放。既往研究表明，omalizumab与IgE的C - epsilon 3结构域结合，该结构域是IgE受体的结合位点，但omalizumab识别的精确表位尚不清楚。在本研究中，我们采用噬菌体展示肽库技术选择与omalizumab结合的肽。该序列与IgE-Fc C - epsilon 3结构域内的序列(HLP426)-H-424同源。我们的结果进一步表明，omalizumab特异性结合IgE-Fc中含有(HLP426)-H-424基序的合成肽“（421）THPHLPRALMRS（432）”。因此，我们得出结论，(HLP426)-H-424基序是omalizumab表位。该表位与高亲和力IgE受体结合位点重叠，从而为omalizumab的作用机制提供了结构基础。(c) 2008爱思唯尔公司版权所有。
Omalizumab is a humanized anti-IgE antibody that inhibits IgE binding to its receptors on mast cells and basophils, thus blocking the IgE-mediated release of pharmacologic mediators from these cells. Previous studies have indicated that omalizumab binds to the C epsilon 3 domain of IgE, which is the binding site of IgE receptors, but the precise epitope recognized by omalizumab is unknown. In this study, we employed the phage display peptide library technology to select peptides binding to omalizumab. A striking peptide sequence motif was recovered, which is homologous to the sequence (HLP426)-H-424 within the C epsilon 3 domain of IgE-Fc. Our results further indicated that omalizumab specifically bound to the synthesized peptide ''(421)THPHLPRALMRS(432)'' containing the (HLP426)-H-424 motif in IgE-Fc. We therefore conclude that the (HLP426)-H-424 motig is the omalizumab epitope. This epitope overlaps with the high-affinity IgE receptor-binding site, thus providing insights into the structural basis for the mechanism of action of omalizumab. (c) 2008 Elsevier Inc. All rights reserved.