Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120.
Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120.
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DOI：
10.4049/jimmunol.150.2.635
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发表时间：
1993-01
影响因子：
4.4
通讯作者：
M. Gorny;Jian-Yin Xu;S. Karwowska;A. Buchbinder;S. Zolla-Pazner
中科院分区：
文献类型：
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作者：
M. Gorny;Jian-Yin Xu;S. Karwowska;A. Buchbinder;S. Zolla-Pazner
HIV感染诱导抗体介导无细胞病毒的中和，并可保护免受病毒感染。结合gp 120的第三高变结构域（V3）的中和人mAb已经从HIV血清阳性受试者的PBL产生。12个这样的mAb识别在V3 MN环的末端跨越11个氨基酸段的9个不同表位。另外两种mAb的表位尚未精确确定，但发生在V3环尖端周围的15-mer肽内。13种mAb中有11种与除MN外的至少一种其他V3肽反应，表明交叉反应性是抗V3抗体中的常见现象。在抗体浓度为12至4700 ng/ml时，所有mAb均达到50%的HIVMN中和。识别V3环顶部表位的两种mAb GPGR和GRAF中和了MN和IIIB等不同菌株。所有检测的mAb对rgp 120的亲和力均显著高于对同源菌株V3环的23-mer肽的亲和力。证明了HIVMN的亲和力和50%中和剂量之间存在显著的负相关性。
HIV infection induces antibodies that mediate neutralization of cell-free virus and may protect against viral infection. Neutralizing human mAb that bind to the third hypervariable domain (V3) of gp120 have been generated from PBL of HIV-seropositive subjects. Twelve such mAb recognize 9 different epitopes spanning an 11 amino acid stretch at the tip of the V3MN loop. The epitopes of an additional two mAb have not been precisely determined but occur within a 15-mer peptide around the tip of the V3 loop. Eleven of 13 mAb are reactive with at least one other V3 peptide besides MN, indicating that cross-reactivity is a common phenomenon amongst anti-V3 antibodies. All the mAb achieved 50% neutralization of HIVMN at antibody concentrations of 12 to 4700 ng/ml. Two mAb, which recognized epitopes at the top of the V3 loop, GPGR and GRAF, neutralized strains as divergent as MN and IIIB. The affinities of all mAb tested were shown to be substantially higher for the rgp120 than for a 23-mer peptide from the V3 loop of the homologous strain. A significant inverse correlation was demonstrated between affinities and the 50% neutralizing doses for HIVMN.