Siliciano R F, Knall C, Lawton T, Berman P, Gregory T, Reinherz E L
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Immunol. 1989 Mar 1;142(5):1506-11.
The HIV envelope glycoprotein gp120 binds with high affinity to CD4 and is responsible for the tropism of HIV for CD4+ T cells and monocytes. Efforts to develop HIV vaccines have focused on gp120 and, therefore, a detailed molecular understanding of human immune responses to gp120 is essential. In this report, we have used human T cell clones specific for gp120 to examine the processing and presentation of gp120 to T cells. In particular, we examined the role of the CD4 that is expressed at low levels on the surfaces of human monocytes in the presentation of gp120 by monocytes. The presentation of gp120 to gp120-specific human T cell clones was blocked by pretreatment of monocytes with anti-CD4 mAb. Blocking of monocyte CD4 with anti-CD4 did not inhibit presentation of other Ag or of synthetic peptides representing epitopes within gp120 recognized by gp120-specific T cell clones. These results indicated that the anti-CD4-mediated inhibition occurred at the level of the monocyte, was specific for the gp120 response, and was operative at the initial Ag uptake phase of the Ag-processing pathway. Definitive confirmation that monocyte CD4 functions in the initial uptake step of the gp120-processing pathway was obtained by using soluble CD4 to block the interaction of gp120 with monocyte CD4. These results demonstrate that gp120 expressed by human monocytes plays an important role in the initial uptake of gp120 by monocytes and that gp120 taken up via CD4 is subsequently processed to allow for exposure of epitopes recognized by gp120-specific human T cells. At limiting gp120 concentrations, uptake via CD4 is essential for the presentation of gp120.
人类免疫缺陷病毒（HIV）包膜糖蛋白gp120与CD4具有高亲和力结合，并且是HIV对CD4+ T细胞和单核细胞具有嗜性的原因。开发HIV疫苗的努力主要集中在gp120上，因此，详细了解人类对gp120的免疫反应的分子机制至关重要。在本报告中，我们使用了对gp120特异的人类T细胞克隆来研究gp120向T细胞的加工和呈递。特别地，我们研究了人类单核细胞表面低水平表达的CD4在单核细胞呈递gp120过程中的作用。用抗CD4单克隆抗体预处理单核细胞可阻断gp120向gp120特异的人类T细胞克隆的呈递。用抗CD4阻断单核细胞CD4并不抑制其他抗原或代表gp120内被gp120特异T细胞克隆识别的表位的合成肽的呈递。这些结果表明，抗CD4介导的抑制发生在单核细胞水平，对gp120反应具有特异性，并且在抗原加工途径的初始抗原摄取阶段起作用。通过使用可溶性CD4阻断gp120与单核细胞CD4的相互作用，最终证实单核细胞CD4在gp120加工途径的初始摄取步骤中发挥作用。这些结果表明，人类单核细胞表达的gp120在单核细胞对gp120的初始摄取中起重要作用，并且通过CD4摄取的gp120随后被加工以允许暴露被gp120特异的人类T细胞识别的表位。在有限的gp120浓度下，通过CD4摄取对于gp120的呈递至关重要。
