Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120
Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120
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DOI：
10.1016/s0092-8674(03)00508-7
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发表时间：
2003-07-25
期刊：
影响因子：
64.5
通讯作者：
Farzan, M
中科院分区：
文献类型：
--
作者：
Choe, H;Li, WH;Farzan, M
主要 HIV-1 辅助受体 CCR5 氨基末端的硫酸化酪氨酸在其结合 HIV-1 包膜糖蛋白 gp120 和介导 HIV-1 感染的能力中发挥着关键作用。在这里，我们发现许多针对 gp120 的人类抗体在其抗原结合位点被酪氨酸硫酸化。与 CCR5 类似，抗体与 gp120 的结合依赖于硫酸盐部分，由 CD4 增强，并由硫酸化 CCR5 衍生肽抑制。这些抗体中的大多数优先与 CCR5 利用 (R5) 分离株的 gp120 分子结合，并且比实验室适应的分离株更有效地中和初级 R5 分离株。这些研究鉴定了 CD4 诱导的 HIV-1 中和抗体的一个独特子集，这些抗体与 CCR5 非常相似，并证明酪氨酸硫酸化可以促进人类体液反应的效力和多样性。
Sulfated tyrosines at the amino terminus of the principal HIV-1 coreceptor CCR5 play a critical role in its ability to bind the HIV-1 envelope glycoprotein gp120 and mediate HIV-1 infection. Here, we show that a number of human antibodies directed against gp120 are tyrosine sulfated at their antigen binding sites. Like that of CCR5, antibody association with gp120 is dependent on sulfate moieties, enhanced by CD4, and inhibited by sulfated CCR5-derived peptides. Most of these antibodies preferentially associate with gp120 molecules of CCR5-utilizing (R5) isolates and neutralize primary R5 isolates more efficiently than laboratory-adapted isolates. These studies identify a distinct subset of CD4-induced HIV-1 neutralizing antibodies that closely emulate CCR5 and demonstrate that tyrosine sulfation can contribute to the potency and diversity of the human humoral response.