鼠抗体OKT3结合位点的结构模拟和改形设计

STRUCTURE MODELING OF MOUSE McAb OKT3 COMBINING SITES AND DESIGN OF HUMANIZED ANTIBODY

使用同源建模的方法通过计算机模拟鼠抗体ＯＫＴ３抗原结合位点的空间结构，在结构分析及人和鼠抗体各自保守序列分析的基础上，设计出抗ＣＤ３的改形抗体序列；并进一步模拟改形抗体的结构，理论计算和实验的结果表明改形设计是合理的。

In order to construct reshaping anti-CD3 antibody, the combining sites of OKT3 weremodeled using the knowledge-based method. On the basis of homology of sequence, humanIg LS1 and ND were selected as acceptors for CDRs of OKT3 VL and VH. By analyzing thetertiary structure of OKT3 and comparing the primary sequence of OKT3, LS1 and ND withtheir own family sequences, some residues in the framework regions were changed and thereshaped VL and VH genes were designed. Also the structural differennces between the originalOKT3 and the reshaped antibody were analyzed. In primary experiment the ashaped antibodyshowed competitive inhibition activities against OKT3 by ELISA.