Lamarre D, Ashkenazi A, Fleury S, Smith D H, Sekaly R P, Capon D J
Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Québec, Canada.
Science. 1989 Aug 18;245(4919):743-6. doi: 10.1126/science.2549633.
CD4 is a cell surface glycoprotein that is thought to interact with nonpolymorphic determinants of class II major histocompatibility (MHC) molecules. CD4 is also the receptor for the human immunodeficiency virus (HIV), binding with high affinity to the HIV-1 envelope glycoprotein, gp120. Homolog-scanning mutagenesis was used to identify CD4 regions that are important in class II MHC binding and to determine whether the gp120 and class II MHC binding sites of CD4 are related. Class II MHC binding was abolished by mutations in each of the first three immunoglobulin-like domains of CD4. The gp120 binding could be abolished without affecting class II MHC binding and vice versa, although at least one mutation examined reduced both functions significantly. These findings indicate that, while there may be overlap between the gp120 and class II MHC binding sites of CD4, these sites are distinct and can be separated. Thus it should be possible to design CD4 analogs that can block HIV infectivity but intrinsically lack the ability to affect the normal immune response by binding to class II MHC molecules.
CD4是一种细胞表面糖蛋白，被认为可与II类主要组织相容性（MHC）分子的非多态性决定簇相互作用。CD4也是人类免疫缺陷病毒（HIV）的受体，能与HIV-1包膜糖蛋白gp120高亲和力结合。同源扫描诱变用于鉴定在II类MHC结合中重要的CD4区域，并确定CD4的gp120和II类MHC结合位点是否相关。CD4前三个免疫球蛋白样结构域中任何一个的突变都会消除II类MHC结合。gp120结合可以在不影响II类MHC结合的情况下被消除，反之亦然，尽管至少一个检测的突变显著降低了这两种功能。这些发现表明，虽然CD4的gp120和II类MHC结合位点可能存在重叠，但这些位点是不同的且可以分开。因此，应该有可能设计出能阻断HIV感染性但本质上缺乏通过与II类MHC分子结合来影响正常免疫反应能力的CD4类似物。
