Healey D G, Dianda L, Beverley P C
Human Tumour Immunology Group, Imperial Cancer Research Fund, London, UK.
J Immunol. 1992 Feb 1;148(3):821-6.
Previous studies have evaluated anti-CD4 mAb as idiotypic models of the HIV gp120-binding site for CD4. The success of this strategy depends upon the concept of internal image, whereby the binding paratope of the anti-CD4 structurally mimics the equivalent binding surface on HIV gp120. To test this concept of internal image, anti-idiotypic antibodies were raised against the anti-CD4, Leu-3a. If any of these anti-Id detect the paratopic idiotope on the anti-CD4 antibody, their own respective paratopes should structurally model the corresponding binding epitope on CD4 bound by Leu-3a. Consequently, the immunization of naive mice with the selected anti-Id should induce an anti-CD4 response which reflects the binding specificities of Leu-3a. Four anti-Id to Leu-3a were characterized and tested for their ability to induce anti-CD4 responses in naive animals. Although one anti-Id induced an anti-CD4 response in mice, no such response could be detected in other species. Thus the failure to raise anti-Id with internal image characteristics may provide an explanation for the lack of anti-gp120 activity reported in anti-Id antisera raised to multiple anti-CD4 antibodies.
以往的研究已将抗CD4单克隆抗体评估为HIV gp120与CD4结合位点的独特型模型。该策略的成功取决于内影像的概念，即抗CD4的结合互补决定簇在结构上模拟HIV gp120上的等效结合表面。为了验证这一内影像概念，制备了针对抗CD4（Leu-3a）的抗独特型抗体。如果这些抗独特型抗体中的任何一种能检测到抗CD4抗体上的互补决定簇独特型表位，那么它们各自的互补决定簇在结构上应模拟Leu-3a所结合的CD4上相应的结合表位。因此，用所选的抗独特型抗体免疫未免疫的小鼠应能诱导出反映Leu-3a结合特异性的抗CD4反应。对4种针对Leu-3a的抗独特型抗体进行了特性鉴定，并测试了它们在未免疫动物中诱导抗CD4反应的能力。虽然有一种抗独特型抗体在小鼠中诱导出了抗CD4反应，但在其他物种中未检测到这种反应。因此，未能产生具有内影像特征的抗独特型抗体可能为针对多种抗CD4抗体产生的抗独特型抗血清中缺乏抗gp120活性提供了解释。
