THE ENVELOPE GLYCOPROTEIN OF THE HUMAN IMMUNODEFICIENCY VIRUS BINDS TO THE IMMUNOGLOBULIN-LIKE DOMAIN OF CD4
THE ENVELOPE GLYCOPROTEIN OF THE HUMAN IMMUNODEFICIENCY VIRUS BINDS TO THE IMMUNOGLOBULIN-LIKE DOMAIN OF CD4
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DOI：
10.1038/334159a0
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发表时间：
1988-07-14
期刊：
影响因子：
64.8
通讯作者：
LITTMAN, DR
中科院分区：
文献类型：
--
作者：
LANDAU, NR;WARTON, M;LITTMAN, DR
CD 4是一种在T细胞和巨噬细胞亚群上表达的细胞表面糖蛋白，作为人类免疫缺陷病毒（HIV）的受体（综述见参考文献1），以高亲和力结合HIV包膜糖蛋白gp 120 2，3。通过产生抗gp 120抗体来阻断体内感染的尝试失败了，可能是因为这些抗体的中和活性不足。此外，由于gp 120在不同的HIV分离株中具有广泛的多态性，因此针对一种HIV分离株的抗体对其他分离株的有效性很弱5。由于与CD 4的相互作用对于所有HIV分离株的感染性都是必不可少的，因此可以模拟CD 4与gp 120结合能力的试剂，如肽或单克隆抗体，可能会阻断广谱分离株的感染。为了帮助识别这样的配体，我们已经定义了与gp 120结合所需的CD 4区域。尽管人CD 4在氨基酸序列（55%同一性，参考文献6）和结构7、8上与小鼠CD 4相似，但我们发现鼠蛋白不能与gp 120可检测地结合，并利用这一发现研究gp 120与小鼠-人嵌合CD 4分子的结合。这些研究表明，人CD 4的氨基末端免疫球蛋白样结构域内的氨基酸残基参与与gp 120以及许多抗CD 4单克隆抗体的结合。
CD4, a cell-surface glycoprotein expressed on a subset of T-cells and macrophages, serves as the receptor for the human immunodeficiency virus (HIV) (reviewed in ref. 1), binding to the HIV envelope glycoprotein, gp120 with high affinity2,3. Attempts to block infectionin vivoby raising antibodies against gp120 have failed, probably because these antibodies have insufficient neutralizing activity4. In addition, because of the extensive polymorphism of gp120 in different isolates of HIV, antibodies raised against one HIV isolate are only weakly effective against others5. Because interaction with CD4 is essential for infectivity by all isolates of HIV, an agent that could mimic CD4 in its ability to bind to gp120, such as a peptide or monoclonal antibody, might block infection by a wide spectrum of isolates. To aid the identification of such a ligand we have defined regions of CD4 that are required for binding to gp120. Although human CD4 is similar to mouse CD4 in amino-acid sequence (55 % identity, ref. 6) and structure7,8, we have found that the murine protein fails to bind detectably to gp120 and have exploited this finding to study binding of gp120 to mouse-human chimaeric CD4 molecules. These studies show that amino-acid residues within the amino-terminal immunoglobulin-like domain of human CD4 are involved in binding to gp120 as well as to many anti-CD4 monoclonal antibodies.