【摘要】 作为一种共受体分子,CD4通过其胞外段与MHCⅡ、TCR相互作用,形成CD4-MHCⅡ-TCR复合物,介导特异性抗原呈递;而其胞质段则通过与酪氨酸激酶P56Lck的相互作用,介导抗原信号传递,最终激活CD4+T细胞,引发一系列的免疫应答。另外,CD4自身的多聚化不仅促进与MHCⅡ、TCR的相互作用,而且增强T细胞抗原识别的特异性和敏感性。因此,通过阻断CD4分子的功能可以达到降低免疫反应性,抑制HIV在机体内复制的目的。随着CD4分子晶体结构的解析,CD4-MHCⅡ、CD4-gp120复合物结构的获得,CD4的功能表位及其结构特征得到合理确认,同时CD4分子与MHCⅡ、gp120作用模式也得到精细分析,以此为理论依据设计的不同类型抗CD4分子的拮抗剂(如抗体、拮抗肽、小分子先导化合物等)越来越得到人们的关注,其中部分拮抗剂已经应用于临床。本综述将对CD4功能表位的确定以及基于其功能表位展开的一系列CD4拮抗分子的研究进行归纳。更多还原

【Abstract】 As a co-receptor, CD4 mediates specific antigen presentation and initiates a series of immunological reactions by forming trimolecular complexes CD4-MHCⅡ-TCR through its ecto-part. The cytoplasmic tail of CD4 is associated with the tyrosine kinase p56lck, which can also activate CD4+ T-cell by antigen signal transmission. Moreover, the self-oligomerization of CD4 not only promotes the stable binding with MHCⅡ and TCR, but also enhances the specificity and sensitivity of antigen recognition by T-cell. Therefore, the immune response can be blocked by inhibition of CD4 function, which can also inhibit the invasion of HIV in organism. Crystallographic studies on CD4 and the complex of CD4-MHCⅡ and CD4-gp120 have indicated the CD4 critical function epitope and the function pattern of CD4-MHCⅡ and CD4-gp120. Some kinds of antagonist (i.e. antibody, antagonist peptide, leading compound,etc.) can be designed based on the structural character of CD4 critical function epitope.Recently, some of them have been used clinically. This article focused on the CD4 function epitope and makes a summary about a series of studies on CD4 antagonists.更多还原