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通过Fc IgG受体I将靶向人类免疫缺陷病毒1型(HIV-1)糖蛋白41的双特异性抗体导向人类巨噬细胞,可介导HIV-1感染中的中和作用。

Bispecific antibody targeting of human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 to human macrophages through the Fc IgG receptor I mediates neutralizing effects in HIV-1 infection.

作者信息

Mabondzo A, Aussage P, Bartholeyns J, Le Naour R, Raoul H, Romet-Lemonne J L, Dormont D

机构信息

Laboratoire de Neuropathologie Expérimentale et Neurovirologie, Service de Santé des Armées, Commissariat à l'Energie Atomique, Fontenay aux Roses, France.

出版信息

J Infect Dis. 1992 Jul;166(1):93-9. doi: 10.1093/infdis/166.1.93.

Abstract

Human monocyte-derived macrophages that express the CD4 molecule and the Fc receptor for IgG (Fc gamma R) play a major role in the pathogenesis of human immunodeficiency virus (HIV) infection. To explore this possibility further, human monoclonal antibody to glycoprotein 41 (gp41) was produced, and a heterobifunctional antibody composed of F(ab') x F(ab')2 fragments of monoclonal anti-gp41 and anti-Fc gamma RI 22.2 were constructed. Both antibodies were analyzed for neutralizing effects, and the role of the CD4 molecule in HIV infection was studied with human monocyte-derived macrophages. The bispecific antibody exhibited strong neutralizing properties, in contrast to the monoclonal anti-gp41 antibody. Moreover, in the presence of monoclonal anti-Leu-3a antibody, viral production was completely inhibited. These findings demonstrate the necessity of the CD4 molecule in HIV infection of human macrophages and emphasize the usefulness of such heterobifunctional antibody directed to virus and monocyte-derived macrophage Fc receptors in prevention of HIV infection.

摘要

表达CD4分子和IgG的Fc受体(FcγR)的人单核细胞衍生巨噬细胞在人类免疫缺陷病毒(HIV)感染的发病机制中起主要作用。为了进一步探究这种可能性,制备了针对糖蛋白41(gp41)的人单克隆抗体,并构建了一种由单克隆抗gp41和抗FcγRI 22.2的F(ab')×F(ab')2片段组成的异双功能抗体。分析了这两种抗体的中和作用,并用人类单核细胞衍生巨噬细胞研究了CD4分子在HIV感染中的作用。与单克隆抗gp41抗体相比,双特异性抗体表现出强大的中和特性。此外,在单克隆抗Leu-3a抗体存在的情况下,病毒产生被完全抑制。这些发现证明了CD4分子在人类巨噬细胞HIV感染中的必要性,并强调了这种针对病毒和单核细胞衍生巨噬细胞Fc受体的异双功能抗体在预防HIV感染中的有用性。

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