近来发现有一些抗体，可特异性识别某些细胞因子并增强其生物活性，被称为增效性抗体。其对细胞因子的活性增强作用有望帮助克服细胞因子在临床使用中因剂量增大而引起的毒副作用，但迄今人们对这种增效性机制了解甚微，使得这种增效性抗体还未得到有效应用。 细胞因子21(IL-21)可调控多种免疫细胞功能，具有抗病毒、抗感染、和抗肿瘤作用，已进入临床实验阶段。我们筛选到一株抗人IL-21的增效性单克隆抗体，对于IL-21介导的体外和体内免疫细胞增殖分化都显示出非常明显的增效作用。我们从分子模拟发现，该增效抗体与非增效抗体相比具有明显不同的抗原结合区。因此，本项目拟以该自主发现的增效抗体为主要研究对象，应用x-射线、核磁共振、免疫表征等多种实验手段首次从分子构象、动力学及信号通路角度研究增效性抗体的增效机理。增效机制的揭示将对未来增效抗体作为疫苗佐剂或独立生物制剂应用到抗肿瘤等实践中提供理论依据。

Accumulating　evidence shows that there are centain antibodies recognizing specific cytokines, that are able to act in an agonistic or even superagonist way by binding to the native molecules. The identity of such antibodies opens up new vistas for the application of antibodies, such as circumventing dose-toxicity effect of cytokine.However,the application of agonistic antibodies is constrained by the limited knowledge of the molecular mechanism underlying their function. We have recently identified an anti-human interlenkin 21(hIL-21) antibody showing superagonistic effects on hIL-21-mediated cell proliferation and activation.IL-21 is a pleiotropic cytokine regulating the function and differentiation of multiple immune cells,and is indispensible for effective antibody response as well as anti-viral,anti-infection, and anti-tumor response.However,how this antibody achieves its superagonistic action is unknown.Accordingly,the broad aim of this work is to perform structural，dynamics，and functional studies on this potentially important agonistic antibody and its target,IL-21.