KINETIC-ANALYSIS OF RECOMBINANT ANTIBODY-ANTIGEN INTERACTIONS - RELATION BETWEEN STRUCTURAL DOMAINS AND ANTIGEN-BINDING
KINETIC-ANALYSIS OF RECOMBINANT ANTIBODY-ANTIGEN INTERACTIONS - RELATION BETWEEN STRUCTURAL DOMAINS AND ANTIGEN-BINDING
复制标题
DOI：
10.1038/nbt0692-697
复制
发表时间：
1992-06-01
期刊：
影响因子：
--
通讯作者：
OHLIN, M
中科院分区：
文献类型：
--
作者：
BORREBAECK, CAK;MALMBORG, AC;OHLIN, M
利用一种基于表面等离子体共振技术的新型生物传感器，首次研究了重组单克隆抗体片段结构域结构与其反应动力学的关系。测定Fab、Fv和单域（VH片段）抗溶菌酶抗体的结合力和解离速率常数，并与完整单克隆抗体进行比较。Fab和Fv片段反应动力学相似，亲和常数分别为6 × 10(9) M-1和25 × 10(9) M-1。单域抗体的反应动力学与由成对的重链和轻链结构域组成的片段有显著不同。VH结构域具有较高的解离率和较低的结合速率常数，其亲和常数比Fab片段低约250倍。当比较抗体片段在治疗或其他应用中的效用时，这种抗体反应动力学的快速评估应该被证明是一个重要的选择参数。
The relation between domain structures of recombinant monoclonal antibody fragments and their reaction kinetics was studied for the first time using a novel biosensor based on surface plasmon resonance technology. The association and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti-lysozyme antibodies were determined and compared to the intact monoclonal antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity constants of 6 x 10(9) M-1 and 25 x 10(9) M-1, respectively. The single domain antibody had significantly different reaction kinetics compared to the fragments consisting of paired heavy and light chain domains. The VH domain had both a higher dissociation and a lower association rate constant, which resulted in an affinity constant approximately 250 times lower than the Fab fragment. This rapid evaluation of antibody reaction kinetics should prove to be an important selection parameter when comparing antibody fragments for their utility in therapeutic or other applications.