HUMAN ANTI-V2 MONOCLONAL-ANTIBODY THAT NEUTRALIZES PRIMARY BUT NOT LABORATORY ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
HUMAN ANTI-V2 MONOCLONAL-ANTIBODY THAT NEUTRALIZES PRIMARY BUT NOT LABORATORY ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
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DOI：
10.1128/jvi.68.12.8312-8320.1994
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发表时间：
1994-12-01
影响因子：
5.4
通讯作者：
ZOLLAPAZNER, S
中科院分区：
文献类型：
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作者：
GORNY, MK;MOORE, JP;ZOLLAPAZNER, S
开发了一种人免疫球蛋白G1 λ单克隆抗体（MAb），697-D，其识别人免疫缺陷病毒1型（HIV-1）gp 120的V2区。在酶联免疫吸附测定形式中，gp 120的V2环中的氨基酸位置176/177、179/180、183/184和192至194处的取代各自完全消除了697-D的结合能力。用三种不同的中和鼠抗V2单克隆抗体进行的竞争分析证实了697-D的特异性。697-D表位主要是构象依赖性的，尽管MAb与跨越残基161至180的V2肽的反应性较弱。治疗的重组gp 120 HIVIIIB与偏高碘酸钠，氧化碳水化合物，废除了单克隆抗体的结合，显示完整的碳水化合物上的表位的依赖性。广泛的反应性697-D显示其结合的gp 120分子从四个实验室分离株和五个主要分离株。MAb 697-D中和了四分之三的原代分离株，但未能中和四种HIV-1实验室菌株中的任何一种，697-D和人抗V3 MAb 447-52-D在中和原代分离株方面表现出相似的效力，表明V2 gp 120的区域，如V3区域和CD 4结合结构域，可以诱导针对人类HN-I的强效中和抗体。
A human immunoglobulin G1 lambda monoclonal antibody (MAb), 697-D, was developed that recognizes the V2 region of human immunodeficiency virus type 1 (HIV-1) gp120. Substitutions at amino acid positions 176/177, 179/180, 183/184, and 192 to 194 in the V2 loop of gp120 each completely abolished the binding capacity of 697-D in an enzyme-linked immunosorbent assay format. Competition analysis with three different neutralizing murine anti-V2 MAbs confirmed the specificity of 697-D. The 697-D epitope is primarily conformation dependent, although there was weak reactivity of the MAb with a V2 peptide spanning residues 161 to 180. Treatment of recombinant gp120 HIVIIIB with sodium metaperiodate, which oxidizes carbohydrates, abolished the binding of the MAb, showing the dependence of the epitope on intact carbohydrates. The broad reactivity of 697-D was displayed by its binding to the gp120 molecules from four of four laboratory isolates and five of five primary isolates. The MAb 697-D neutralized three out of four primary isolates but failed to neutralize any of four laboratory strains of HIV-1, 697-D and a human anti-V3 MAb, 447-52-D, displayed similar potency in neutralizing primary isolates, indicating that the V2 region of gp120, like the V3 region and the CD4-binding domain, can induce potent neutralizing antibodies against HN-I in humans.