Studies on the mechanism of Cytotoxic T-lymphocyte (CTL)-mediated muscle breakdown

肌病肌肉中结构蛋白降解的机制尚不完全清楚。本文从t淋巴细胞杀伤分子的功能角度对其进行了研究。在2年的研究项目中，我们发现：1)细胞毒性t淋巴细胞（CTL）中的细胞毒颗粒含有两种不同的裂解分子，穿孔素和丝氨酸酯酶（SE）。穿孔素由CTL膜上的受体发出信号后释放，首先与靶细胞膜结合，随后在同一膜上形成功能性孔。这些过程需要Ca^<2+ bbb100离子。肝素和其他酸性粘多糖只是增强了成孔的裂解过程。2)我们发现SE在CTL细胞中的定位与穿孔素的定位不同。SE不消化肌球蛋白，而其他细胞质蛋白酶消化肌球蛋白。提示SE不直接参与ctl介导的蛋白降解。3)分离纯化了两种新型蛋白水解酶，一种是高分子质量多催化蛋白酶——人参素，另一种是胱氨酸氨基肽酶。芦荟素被证明参与atp依赖性蛋白水解。

The mechanism by Which structural proteins in myopathic muscle are degraded is not fully understood. This work focused on the killing molecules in T-lymphocytes from the viewpoint of their functions. During 2 years of research project, we found the following:1) Cytotoxic granules in cytotoxic T-lymphocytes (CTL) contain two distinct lytic molecules, perforin and serine esterase (SE). Perforin, which is released after signalling by a receptor on the CTL membrane, first binds to the target cell membrane and subsequently forms functional pore on the same membrane. These processes require Ca^<2+>ions. Heparin and other acid mucopolysaccharides only enhanced the pore-forming lytic process.2) We found that localization of SE is different from that of perforin in CTL cells. SE did not digest myosin, whereas other cytoplasmic protease digested it. Suggesting that SE is not directly involved in CTL-mddiated protein degradation.3) We isolated and purified two novel proteolytic enzymes, one is a high-molecular-mass multicatalytic proteinase, ingensin, and the other cystine aminopeptidase. Ingensin was shown to be involved in ATP-dependent proteolysis.