传统的化疗可使大多数B细胞淋巴瘤患者暂时缓解，但复发仍是临床治疗的难点。前期研究中，我们首先发现T细胞白血病/淋巴瘤抗原1(TCL1)在多种B细胞淋巴瘤中特异性高表达，而TCL1介导的细胞毒性T细胞可以靶向杀死B细胞淋巴瘤而对正常B细胞无影响。本项目将克隆TCL1特异性野生型和变异型单链T细胞受体(scTCR)，检测scTCR在正常T细胞中的表达以及和多肽/MHC分子的结合力；检测scTCR介导T细胞对抗原特异性的识别；检测被scTCR基因修饰T细胞的细胞因子释放情况以及对淋巴瘤的细胞毒反应；具有杀伤功能的scTCR基因修饰T细胞过续性转导入小鼠体内观察T细胞对B细胞淋巴瘤的杀伤作用。从而获得TCL1特异性scTCR，阐明scTCR介导T细胞杀伤B淋巴瘤细胞的机制。

Traditional chemotherapy can temporarily induce complete remission in the majority of patients with B-cell lymphomas, but relapse remains the difficulty of clinical management. In the preliminary study, we first discovered the T-cell leukemia/lymphoma antigen 1 (TCL1) specifically and highly expressed in a variety of B-cell lymphomas. TCL1 stimulated cytotoxic T cells that can specifically target B-cell lymphomas but not normal B cells. Here we propose to clone TCL1-specific wilde-type and mutant single-chain T-cell receptor (scTCR). The expression of scTCR in normal T cells and the binding affinity of scTCR with the peptide/MHC will be analyzed in vitro. The specific recognition of antigen by scTCR will be tested in vitro. After that, the scTCR-transduced T cells will be tested for cytokines secretion and cytotoxicity against B-cell lymphomas in vitro. Finally, the cytotixic scTCR-transduced T cells will be adoptively transferred in vivo to test the ability to lyse the B-cell lymphomas. Successful completion of this project will help acquire TCL1 specific scTCR and elucidate the mechanism of specific cytotoxicity mediated by scTCR.