Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120.
Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120.
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CD4 的寡聚化是与 II 类主要组织相容性复合体蛋白稳定结合所必需的，但与人类免疫缺陷病毒 gp120 相互作用则不需要。
DOI：
10.1073/pnas.92.14.6444
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发表时间：
1995
影响因子：
11.1
通讯作者：
Reinherz,EL
中科院分区：
文献类型：
--
作者：
Sakihama,T;Smolyar,A;Reinherz,EL
先前的研究未能检测到单体可溶性 CD4 (sCD4) 和 II 类主要组织相容性复合体 (MHC) 蛋白之间的相互作用，这表明可能需要细胞表面 CD4 的寡聚化来形成稳定的 II 类 MHC 结合位点。为了测试这种可能性，我们将无法与 II 类 MHC 或人类免疫缺陷病毒 (HIV) gp120 结合的 F43I CD4 突变体与野生型 CD4 (wtCD4) 一起转染到 COS-7 细胞中。 F43I 的表达导致显性负效应：尽管保留了 wtCD4 表达，但未观察到 II 类 MHC 结合。显然，F43I 与 wtCD4 寡聚体结合并干扰功能性 II 类 MHC 结合结构的形成。相反，F43I 不影响 gp120 与 wtCD4 的结合，这意味着 gp120 与 CD4 单体结合。通过嵌合 CD4 分子的产生和表征，我们表明结构域 3 和/或 4 似乎参与寡聚化。提供了几种 CD4-II 类 MHC 相互作用的模型，包括一个或两个 CD4 分子最初与 II 类 MHC 二聚体相互作用并进一步结合形成对促进 T 细胞受体交联重要的更大复合物的可能性。
Previous studies have failed to detect an interaction between monomeric soluble CD4 (sCD4) and class II major histocompatibility complex (MHC) proteins, suggesting that oligomerization of CD4 on the cell surface may be required to form a stable class II MHC binding site. To test this possibility, we transfected the F43I CD4 mutant, which is incapable of binding to class II MHC or human immunodeficiency virus (HIV) gp120, into COS-7 cells together with wild-type CD4 (wtCD4). Expression of F43I results in a dominant negative effect: no class II MHC binding is observed even though wtCD4 expression is preserved. Apparently, F43I associates with wtCD4 oligomers and interferes with the formation of functional class II MHC binding structures. In contrast, F43I does not affect the binding of gp120 to wtCD4, implying that gp120 binds to a CD4 monomer. By production and characterization of chimeric CD4 molecules, we show that domains 3 and/or 4 appear to be involved in oligomerization. Several models of the CD4-class II MHC interaction are offered, including the possibility that one or two CD4 molecules initially interact with class II MHC dimers and further associate to create larger complexes important for facilitating T-cell receptor crosslinking.