Binding Activity Difference of Anti-CD20 scFv-Fc Fusion Protein Derived from Variable Doma

Binding Activity Difference of Anti-CD20 scFv-Fc Fusion Protein Derived from Variable Domain

Exchange

Shusheng

Geng;Beifen

Shen;Jiannan

Li;Yingxun

Sun;Xin

Gu;Ying

Feng;Yan

Huang;Yugang Wang;Xianjiang Kang;Hong Chang

【期刊名称】《中国免疫学杂志（英文版）》 【年(卷),期】2006(003)006

【摘要】Two novel engineered antibody fragments binding to antigen CD20 were generated by fusing a murine IgM-type anti-CD20 single-chain Fv fragment (scFv) to the human IgG1 CH2 (I.e., Cγ2) and CH3 (I.e., Cγ3) domains with the human IgG1 hinge (I.e. Hγ). Given the relationship between structure and function of protein, the 3-D structures of the two engineered antibody fragments were modeled using computer-aided homology modeling method.Furthermore, the relationship between 3-D conformation and their binding activity was evaluated theoretically.Due to the change of active pocket formed by CDRs, the HL23 (VH-Linker-VL-Hγ-Cγ2-Cγ3) remained its activity because of its preserved conformation, while the binding activity of the LH23 (VL-Linker-VH-Hγ-Cγ2-Cγ3) was impaired severely. Experimental studies by flow cytometry and fluorescence microscopy showed that HL23 possessed significantly superior binding activity to CD20-expressing target cells than LH23. That is to say, the order of variable

regions could influence the binding activity of the fusion protein to CD20+ cell lines, which was in accordance with the theoretical results. The study highlights the potential relationship between the antibody binding activity and their 3-D conformation, which appears to be worthwhile in providing direction for future antibody design of recombinant antibody. 【总页数】5页(439-443)

【关键词】binding activity, scFv-Fc, variable domain exchange, molecular modeling

【作者】Shusheng Geng;Beifen Shen;Jiannan Feng;Yan Li;Yingxun Sun;Xin Gu;Ying Huang;Yugang Wang;Xianjiang Kang;Hong Chang 【作者单位】College of Life Science, Hebei University, Baoding, Hebei, China;Institute of Basic Medical Sciences, Beijing, China;These authors contributed equally to this work;Institute of Basic Medical Sciences, Beijing, China ;Institute of Basic Medical Sciences, Beijing, China;Lab of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng, Henan, China;These authors contributed equally to this work;Institute of Basic Medical Sciences, Beijing, China;Lab of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng, Henan, China;These authors contributed equally to this work;Institute of Basic Medical Sciences, Beijing, China ;Institute of Basic Medical Sciences, Beijing, China ;Institute of Basic Medical Sciences,

Beijing, China ;Institute of Basic Medical Sciences, Beijing, China ;College of Life Science, Hebei University, Baoding, Hebei, China;Institute of Basic Medical Sciences, Beijing, China 【正文语种】中文 【中图分类】R3 【文献来源】

https://www.zhangqiaokeyan.com/academic-journal-cn_cellular-molecular-immunology_thesis/0201224017737.html 【相关文献】

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