Scott C F, Silver S, Profy A T, Putney S D, Langlois A, Weinhold K, Robinson J E
Repligen Corporation, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8597-601. doi: 10.1073/pnas.87.21.8597.
We describe a human IgG1 monoclonal antibody (N701.9b) derived by Epstein-Barr virus transformation of B cells from a human immunodeficiency virus-seropositive asymptomatic donor. This antibody was shown to recognize the principal neutralizing domain contained within the V3 region of gp120 of the MN strain of human immunodeficiency virus and MN-like strains, as determined by binding to the PB-1 fragment of MN gp120 and to synthetic peptides corresponding to the V3 region of MN and related virus strains. The epitope identified by monoclonal antibody N701.9b was mapped to a segment of V3 containing at least 7 amino acids (amino acids 316-322), which is located in the "tip" and "right" side of the V3 loop of the MN strain. Furthermore, this antibody manifested potent type-specific fusion-inhibitory activity against the MN strain but not against the IIIB or RF virus strains. This antibody also neutralized four virus isolates that had MN-like V3 region sequences and failed to neutralize three other strains containing unrelated V3 region sequences. Our findings confirm that the V3 region stimulates type-specific neutralizing antibody during natural human immunodeficiency virus infection in humans. The potential clinical use of this antibody is discussed.
我们描述了一种人IgG1单克隆抗体(N701.9b),它是通过对来自一名人类免疫缺陷病毒血清反应阳性无症状供体的B细胞进行爱泼斯坦-巴尔病毒转化而获得的。通过与MN gp120的PB-1片段以及与对应于MN和相关病毒株V3区域的合成肽结合,确定该抗体可识别人类免疫缺陷病毒MN株和MN样株gp120的V3区域内包含的主要中和结构域。单克隆抗体N701.9b识别的表位被定位到V3的一段至少包含7个氨基酸(氨基酸316 - 322)的区域,该区域位于MN株V3环的“顶端”和“右侧”。此外,该抗体对MN株表现出有效的型特异性融合抑制活性,但对IIIB或RF病毒株则无此活性。该抗体还中和了4株具有MN样V3区域序列的病毒分离株,而未能中和另外3株含有不相关V3区域序列的病毒株。我们的研究结果证实,V3区域在人类自然感染人类免疫缺陷病毒期间刺激型特异性中和抗体产生。本文还讨论了该抗体的潜在临床应用。