Specificity tuning of antibody fragments to neutralize two human chemokines with a single agent
Specificity tuning of antibody fragments to neutralize two human chemokines with a single agent
复制标题
DOI：
10.4161/mabs.1.3.8527
复制
发表时间：
2009-05-01
期刊：
影响因子：
5.3
通讯作者：
Fischer, Nicolas
中科院分区：
文献类型：
--
作者：
Fagete, Severine;Ravn, Ulla;Fischer, Nicolas
趋化因子是免疫反应的重要介质，负责免疫细胞在淋巴器官之间的运输和向炎症部位的迁移。通过噬菌体展示筛选和功能筛选的方法，我们分离到一组能够中和人趋化因子CXCL10(HCXCL10)活性的单链片段变量(ScFv)。其中一株单链抗体与另一种人趋化因子CXCL9有弱交叉反应，但不能阻断其生物学活性。我们使该单链抗体轻链可变区(VL)的互补决定区3(CDR3)多样化，并结合噬菌体展示和高通量抗体阵列筛选来识别能够中和两种趋化因子的变体。因此，使用这种方法有可能设计出泛特异性抗体，这种抗体可能被证明对对抗多余的信号通路非常有用，例如趋化因子信号网络。
Chemokines are important mediators of the immune response that are responsible for the trafficking of immune cells between lymphoid organs and migration towards sites of inflammation. Using phage display selection and a functional screening approach, we have isolated a panel of single-chain fragment variable (scFv) capable of neutralizing the activity of the human chemokine CXCL10 (hCXCL10). One of the isolated scFv was weakly cross-reactive against another human chemokine CXCL9, but was unable to block its biological activity. We diversified the complementarity determining region 3 (CDR3) of the light chain variable domain (VL) of this scFv and combined phage display with high throughput antibody array screening to identify variants capable of neutralizing both chemokines. Using this approach it is therefore possible to engineer pan-specific antibodies that could prove very useful to antagonize redundant signaling pathways such as the chemokine signaling network.