Takeda A, Robinson J E, Ho D D, Debouck C, Haigwood N L, Ennis F A
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
J Clin Invest. 1992 Jun;89(6):1952-7. doi: 10.1172/JCI115802.
There is increasing evidence that sera from HIV-1-infected individuals contain antibodies that enhance infection by HIV-1 in vitro. Previous work has demonstrated that complement receptors on T lymphoid cells and Fc receptors for IgG (Fc gamma R) on monocytic cells are required for enhanced infection by antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from HIV-1 vaccines. This study was conducted to identify enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV-1, which were produced by B cell lines derived from an HIV-1-infected individual. A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but had little neutralizing activity. A competition radio immunoassay demonstrated that the two antibodies bind to distinct epitopes. These results indicated that enhancing and neutralizing antibodies can be induced by different epitopes on gp120, suggesting the potential for development of safe vaccines against HIV-1 by exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to identify the epitope on gp120 that is recognized by the enhancing antibody N70-2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of gp120.
越来越多的证据表明，来自HIV-1感染者的血清中含有能在体外增强HIV-1感染的抗体。先前的研究表明，T淋巴细胞上的补体受体和单核细胞上的IgG Fc受体（FcγR）是抗体复合的HIV-1增强感染所必需的。鉴定这种感染增强抗体至关重要，因为诱导增强抗体的免疫原性表位应被排除在HIV-1疫苗之外。本研究旨在利用针对HIV-1 gp120的IgG人单克隆抗体（HMAb）来鉴定参与Fc R介导的HIV-1感染增强的增强抗体，这些抗体由源自一名HIV-1感染者的B细胞系产生。一种有效的中和HMAb N70-1.5e不会增强HIV-1（IIIB和MN毒株）的感染，而HMAb N70-2.3a介导HIV-1感染的增强，但中和活性很小。竞争放射免疫分析表明这两种抗体结合不同的表位。这些结果表明，增强抗体和中和抗体可由gp120上不同的表位诱导产生，这提示通过排除增强抗体的免疫原性表位来开发安全的HIV-1疫苗具有潜力。我们试图通过使用重组HIV-1蛋白来鉴定增强抗体N70-2.3a识别的gp120上的表位，结果发现该抗体结合gp120羧基端一半（aa 272-509）非可变序列的一个构象位点。
