A novel membrane-bound serine protease in human T4^+-lymphocyte -possible receptor for HIV gp120-

人类免疫缺陷病毒(HIV)感染是由于HIV的包膜糖蛋白(Gp120)与存在于T4^+淋巴细胞表面的CD4分子相互作用而介导的病毒-细胞融合。然而，CD4分子可能不是HIV受体的唯一成分，因为表达人类CD4分子的小鼠细胞不会感染HIV。我们最近在人类T4^+淋巴细胞中发现了一种新的膜结合丝氨酸蛋白酶，命名为类胰蛋白酶TL2，它与HIV gp120的V3结构域特异结合。该酶的相对分子质量为198 KDa，由32 KDa的两个亚基和28 KDa的四个亚基组成。细胞表面放射性碘标记表明，32 KDa亚基暴露在T淋巴细胞表面，并与HIV gp120的V3结构域结合。Scatchard分析表明，类胰蛋白酶TL2上只有一类gp120结合位点，其表观解离常数为3.8×10~(-8)&gt；M。据报道，V3结构域是HIV的主要中和决定因素，也是HIV感染的细胞嗜性的决定因素。针对V3结构域的抗体和针对类胰蛋白酶TL2的抗体、类胰蛋白酶Konitz型抑制剂TL2的抗体以及合成的各种V3结构域的多肽。HIV株有效地抑制了gpl2O与类胰蛋白酶TL2的结合。这些抗体、抑制剂和多肽也能抑制HIV诱导的合胞体形成。这些结果表明，在HIV感染的初始过程中，类胰蛋白酶TL2在HIV的靶点识别和结合中起重要作用。类胰蛋白酶TL2在与CD4受体协同的膜融合过程中的作用的研究正在进行中

Infection by human immunodeficiency virus (HIV) is due to virus-cell fusion mediated by interaction of the envelope glycoprotein (gp120) of HIV with the CD4 molecule present on the surface of T4^+ lymphocytes. However, the CD4 molecule may not be the only component of HIV receptor because mouse cells expressing the human CD4 molecule are not infected by HIV. We recently found a novel membrane-bound serine protease, named tryptase TL2, other than CD4 receptor in human T4^+ lymphocytes which specifically binds the V3 domain of HIV gp120. The enzyme has a molecular mass of 198KDa and is composed of two subunits of 32KDa and four subunits of 28KDa. Cell surface radioiodination indicated that the subunit of 32KDa is exposed on the surface of T lymphocyte and binds to the V3 domain of HIV gp120. Scatchard analysis revealed a single class of gp120 binding site on tryptase TL2 with an apparent dissociation constant of 3.8 x 10^<-8>M for tryptase TL2. The V3 domain has been reported to be the principal neutralizing determinant of HIV and also to be a determinant for cellular tropism of HIV infection. Antibody against the V3 domain and that against tryptase TL2, kunitz-type inhibitors of tryptase TL2 and synthetic V3 domain peptides of various. HIV strains effectively inhibited the binding of gpl2O to tryptase TL2. These antibodies, the inhibitors and the peptides also inhibited syncytia formation induced by HIV. These results suggest that Tryptase TL2 is important in target site recognition and binding of HIV in the initial process of HIV infection. The studies on the role of tryptase TL2 in the process of membrane fusion in co-operation with CD4 receptor is now in progress