Nakamura G R, Byrn R, Rosenthal K, Porter J P, Hobbs M R, Riddle L, Eastman D J, Dowbenko D, Gregory T, Fendly B M
Department of Immunobiology, Genentech, Inc., S. San Francisco, CA 94080.
AIDS Res Hum Retroviruses. 1992 Nov;8(11):1875-85. doi: 10.1089/aid.1992.8.1875.
Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library.
对针对源自HIV-1 IIIB分离株的可溶性重组gp160制备的10种单克隆抗体进行了表征。其中4种抗体在体外中和了HIV-1 IIIB的感染性，3种阻断了重组gp120与CD4的结合，3种与gp41反应，1种优先与gp160前体中gp120上的一个表位反应。所有3种CD4阻断抗体均与不同的表位结合，其中一种定位到C1结构域，一种定位到C4结构域，一种与一个构象依赖性的不连续表位反应。其中，与不连续表位反应的抗体对HIV-1的同源和异源毒株均表现出中和活性。测定了这些单克隆抗体与由HIV-1不同分离株制备的一组7种重组gp120的结合情况，并鉴定出具有广泛交叉反应性的单克隆抗体。通过研究的10种单克隆抗体中的7种与合成肽以及在λgt-11 gp160表位文库中作为融合蛋白表达的gp120片段的反应性，定位了它们识别的表位。
