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HIV-1感染患者中的大多数中和抗体识别线性V3环序列。使用HIV-1MN多种抗原肽的研究。

The majority of neutralizing Abs in HIV-1-infected patients recognize linear V3 loop sequences. Studies using HIV-1MN multiple antigenic peptides.

作者信息

Vogel T, Kurth R, Norley S

机构信息

Paul Ehrlich Institute, Langen, Germany.

出版信息

J Immunol. 1994 Aug 15;153(4):1895-904.

PMID:7519220
Abstract

Multiple antigenic peptides (MAP) comprising eight synthetic peptides corresponding to the V3 loop of HIV-1MN or HIV-1IIIB linked to a lysine core were used to characterize the humoral Ab response of HIV-1-infected patients against this domain. One hundred percent of the tested sera from HIV-1-infected European patients reacted significantly with the HIV-1MN V3 loop MAP. Most, but not all, sera also reacted against the HIV-1IIIB V3 loop MAP, albeit with low titers. The in vitro neutralization capacity of the patients' sera against HIV-1MN or HIV-1IIIB infection were tested. All sera showed significant neutralizing titers against HIV-1MN, in comparison with the low (when detectable) neutralizing titers against HIV-1IIIB. Competition assays revealed that the majority of HIV-1MN-neutralizing Abs in patients' sera react with the V3 loop peptides. Only a small fraction of the total neutralizing capacity, presumably specific for other neutralizing epitopes, could not be adsorbed with HIV-1MN V3 loop peptides. The V3 loop peptides could also compete for the binding of Abs in patients' sera mediating Ab-dependent cellular cytotoxicity (ADCC) of HIV-1MN infected cells, inhibiting 30 to 80% of the ADCC activity. Finally, the HIV-1MN V3 loop MAP, when used as immunogen in the presence of RIBI adjuvant without a carrier protein, elicited Abs able to neutralize HIV-1MN (but not HIV-1IIIB) and to initiate ADCC of HIV-1MN-infected cells. This neutralizing and ADCC activity, mediated by V3MN-specific rabbit Abs, could be totally absorbed by V3MN loop peptides.

摘要

包含与赖氨酸核心相连的对应于HIV-1MN或HIV-1IIIB V3环的八个合成肽的多抗原肽(MAP)被用于表征HIV-1感染患者针对该区域的体液抗体反应。来自感染HIV-1的欧洲患者的100%检测血清与HIV-1MN V3环MAP有显著反应。大多数(但不是全部)血清也与HIV-1IIIB V3环MAP反应,尽管滴度较低。测试了患者血清对HIV-1MN或HIV-1IIIB感染的体外中和能力。与针对HIV-1IIIB的低中和滴度(可检测时)相比,所有血清对HIV-1MN均显示出显著的中和滴度。竞争试验表明,患者血清中大多数HIV- MN中和抗体与V3环肽反应。总中和能力中只有一小部分(可能针对其他中和表位)不能被HIV-1MN V3环肽吸附。V3环肽也可以竞争患者血清中抗体与HIV-1MN感染细胞的抗体依赖性细胞毒性(ADCC)介导的结合,抑制30%至80%的ADCC活性。最后,当HIV-1MN V3环MAP在没有载体蛋白的情况下与RIBI佐剂一起用作免疫原时,可引发能够中和HIV-1MN(但不能中和HIV-1IIIB)并启动HIV-1MN感染细胞ADCC的抗体。由V3MN特异性兔抗体介导的这种中和和ADCC活性可被V3MN环肽完全吸收。

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