Mann D L, Read-Connole E, Arthur L O, Robey W G, Wernet P, Schneider E M, Blattner W A, Popovic M
Section of Biochemical Epidemiology, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1988 Aug 15;141(4):1131-6.
The primary interaction of HIV-1 with the target cell involves the viral large envelope protein (gp120) and the cellular CD4 molecule. mAb reacting with portions of CD4 have been shown to block HIV-1 attachment and infection. In one of the early reports describing HIV-1 cell interaction, some mAb reacting with MHC class II Ag were also found to block infection. To investigate further a possible role for MHC class II in HIV-1 binding, a cultured T lymphocyte cell line (H-9) that expresses MHC class II molecules and PHA-stimulated PBL was exposed for various time periods to concentrated viral particles and individual HIV-1 proteins. A decrease in the ability to detect the CD4a epitope and HLA-DR was observed after the cells were exposed to virus for 15, 30, and 60 min whereas HLA-DP and HLA-DQ Ag increased or remained unchanged. After 120 min of virus exposure, the CD4a epitope remained diminished whereas HLA-DR was detected at levels found on cells not exposed to virus. mAb detecting the CD4a epitope and HLA-DR, as well as alloantisera detecting the specific HLA-DR Ag on the target cell, blocked HIV-1 binding. When immunopurified gp120 was added to PHA-stimulated and unstimulated PBL, the CD4a epitope decreased in the same manner as was observed with whole virus preparations. In contrast to exposure to the intact virus, HLA-DR expression appeared to increase. Other viral proteins, p17, p24, and a portion of the small envelope protein, gp41, had no effect on the ability to detect cell surface Ag. Thus, although CD4 is the primary receptor for HIV-1 binding, HLA-DR appears to be involved in the binding site, probably by virtue of its close proximity to the CD4 molecule on the cell surface.
HIV-1与靶细胞的主要相互作用涉及病毒大包膜蛋白（gp120）和细胞CD4分子。已证明与CD4部分发生反应的单克隆抗体可阻断HIV-1的附着和感染。在早期描述HIV-1与细胞相互作用的一份报告中，还发现一些与MHC II类抗原发生反应的单克隆抗体也可阻断感染。为了进一步研究MHC II类在HIV-1结合中的可能作用，将表达MHC II类分子的培养T淋巴细胞系（H-9）和PHA刺激的外周血淋巴细胞（PBL）在不同时间段暴露于浓缩病毒颗粒和单个HIV-1蛋白。细胞在暴露于病毒15、30和60分钟后，检测CD4a表位和HLA-DR的能力下降，而HLA-DP和HLA-DQ抗原增加或保持不变。病毒暴露120分钟后，CD4a表位仍然减少，而HLA-DR在未暴露于病毒的细胞上检测到的水平上被检测到。检测CD4a表位和HLA-DR的单克隆抗体，以及检测靶细胞上特异性HLA-DR抗原的同种抗血清，均可阻断HIV-1的结合。当将免疫纯化的gp120添加到PHA刺激和未刺激的PBL中时，CD4a表位以与全病毒制剂相同的方式减少。与暴露于完整病毒相反，HLA-DR表达似乎增加。其他病毒蛋白，p17、p24和小包膜蛋白gp41的一部分，对检测细胞表面抗原的能力没有影响。因此，尽管CD4是HIV-1结合的主要受体，但HLA-DR似乎参与了结合位点，可能是由于其在细胞表面与CD4分子的紧密接近。
