研究证实NK细胞通过CD16介导的ADCC在控制病毒感染和肿瘤免疫治疗中发挥着重要作用，但其在HBV感染中的作用至今尚未阐明。T细胞受体样抗体（TCRL-Ab）能高度模拟TCR，特异性识别HBV感染肝细胞表面抗原肽-MHC复合物。我们前期研究发现TCRL-Ab可介导NK细胞ADCC，且慢性HBV感染者NK细胞CD16表达下降从而导致其ADCC效能降低。我们推测TCRL-Ab介导NK细胞的ADCC能有效控制病毒，通过恢复NK细胞CD16表达可增强其ADCC效应以提高抗病毒能力。本课题拟借助TCRL-Ab研究NK细胞ADCC在慢性HBV感染中的作用以及其与疾病预后的关系，分析影响此效应的因素，并通过体外实验和动物模型探讨恢复慢性HBV感染者NK细胞CD16表达是否能增强ADCC在病毒控制中的作用。本研究有助于阐明NK细胞ADCC在慢性HBV感染中的作用并为探索乙肝免疫治疗新策略提供理论依据。

Previous studies have shown that antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells plays an important role in the control of virus infection and cancer immunotherapy. However, the role of ADCC in HBV infection remains unclear. Newly generated T-cell receptor-like antibody (TCRL-Ab) can authentically mimic TCR specificity and recognize peptide/major histocompatibility complex (pMHC) complexes present on the surface of HBV infected hepatocytes. Our preliminary work have found that such TCRL-Ab can mediate ADCC activity of NK cells and the density of CD16 on NK cells was significantly reduced in patients with chronic HBV infection, which resulted in impaired capacity of ADCC. Hence, we speculated that TCRL-Ab mediated ADCC of NK cells may contribute to effective control of HBV replication, and restoration of CD16 expression on NK cells from patients with chronic HBV infection may enhance ADCC activity, thus improve the antiviral ability of NK cells. By virtue of such TCRL-Ab, current research aims to investigate the characteristic of ADCC mediated by NK cells in chronic HBV infection and to analyze potential factors that exert influence on ADCC capacity. In addition, the effect of restoration of CD16 expression on NK cells from patients with chronic HBV infection on ADCC capacity in suppressing HBV replication will be explored in mouse model and in vitro experiments. This study will not only help to clarify the function of ADCC mediated by NK cells in chronic HBV infection, but also provide theoretical evidence for the rational development of new immunotherapeutic strategy for the management of chronic HBV infection.