Krähenbühl O, Tschopp J
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Nat Immun Cell Growth Regul. 1990;9(4):274-82.
Cytolytic T lymphocytes (CTL) and large granular lymphocytes contain dense cytoplasmic granules which, when isolated, are lytic for a variety of target cells. Granule proteins are released from the effector cell upon target cell interaction, further suggesting that they play a role in the cytolytic mechanism. Major proteins in CTL granules are a family of serine esterases (granzymes) and a pore-forming protein called perforin (cytolysin). Despite structural similarities between functionally conserved regions of perforin and the ninth component of complement (C9), these two lytic molecules are clearly distinct in their mode of target cell recognition. Perforin, unlike C9, is not dependent on a protein receptor molecule but binds to the target cell membrane via phosphorylcholine in a Ca2(+)-dependent manner. Here, we discuss the stimulus-secretion model for T-cell-mediated cytotoxicity with respect to our current understanding of perforin and the granzyme proteases.
细胞毒性T淋巴细胞（CTL）和大颗粒淋巴细胞含有致密的细胞质颗粒，分离这些颗粒时，它们对多种靶细胞具有溶解性。颗粒蛋白在效应细胞与靶细胞相互作用时从效应细胞中释放出来，这进一步表明它们在细胞溶解机制中发挥作用。CTL颗粒中的主要蛋白质是丝氨酸酯酶家族（颗粒酶）和一种称为穿孔素（细胞溶素）的成孔蛋白。尽管穿孔素功能保守区域与补体第九成分（C9）在结构上有相似之处，但这两种溶解分子在靶细胞识别模式上明显不同。与C9不同，穿孔素不依赖于蛋白质受体分子，而是以Ca2(+)依赖的方式通过磷酸胆碱与靶细胞膜结合。在此，我们结合目前对穿孔素和颗粒酶蛋白酶的了解，讨论T细胞介导的细胞毒性的刺激-分泌模型。
