EPITOPE MAPPING OF HIV-1 ENHANCING ANTIBODIES

人类感染者血清中的频繁检出 免疫缺陷病毒(HIV-1)的抗体增强了传染性 已经报告了HIV-1(EAB)的感染。这类血清中的EAB水平通常 超过病毒中和抗体(VNAb)水平。另一方面 另一方面，一些抗HIV-1阳性血清含有VNAb，但没有检测到 EAB，表明VNAb和EAB识别不同的表位 HIV-1囊膜糖蛋白(gp120和gp41)。期间生成的EAB HIV-1感染。用gp120/gp41免疫诱导的EAB可 削弱或取消其他抗体的保护作用 参与艾滋病毒-=1的中和和消除艾滋病毒-1和 HIV-1感染细胞。HIV-1保护性免疫原的设计将是 促进：(1)识别EAB识别的表位和(2) 了解病毒增强的机制。 我们建议定义gp120/gp41表位参与增强HIV- 1单核细胞感染性使用：(A)抗肽抗血清和(B) 从人抗HIV阳性血清中分离特异性抗体 与固体相连的不同合成肽的亲和层析 支持。建议研究的试剂是可用的(5)肽 (19-26个氨基酸残基)从几乎全长的gp120 和gp41及相应的抗血清。在建立了 传染性HIV-1抗体进入部位EAB的特异性 (AB)进入细胞的复合体将通过以下抑制物定义 抗HIV-1的CD4(T4)受体抗体的作用；(B)Fc 受体；和(C)补体C3b受体 HIV-1抗体复合体和β)在缺乏情况下对gp120/gp41的摄取 以及具有定义的表位特异性的EAB的存在。

The frequent detection in sera of humans infected with the human immunodeficiency virus (HIV-1) of antibodies enhancing the infectivity of HIV-1 (EAb) has been reported. The level of EAb in such sera usually exceeded the level of virus-neutralizing antibodies (VNAb). On the other hand, some anti-HIV-1 positive sera contained VNAb but no detectable EAb, suggesting that VNAb and EAb recognize distinct epitopes on the envelope glycoproteins (gp120 and gp41) of HIV-1. EAb generated during HIV-1 infection. EAb elicited by immunization with gp120/gp41 may diminish or abrogate the protective efficacy of other antibodies involved in HIV-=1 neutralization and in elimination of HIV-1 and of HIV-1 infected cells. The design of HIV-1 protective immunogens will be facilitated by: (1) identification of epitopes recognized by EAb and (2) understanding the mechanism of virus enhancement. We propose to define gp120/gp41 epitopes involved in enhancement of HIV- 1 infectivity for monocytes using: (a) anti-peptide antisera and (b) specific antibodies isolated from human anti HIV-positive sera by affinity chromatography on distinct synthetic peptides linked to a solid support. Reagents for the proposed research are available (5) peptides (19-26 amino acid residues long) from nearly the entire length of gp120 and gp41 and the corresponding antisera]. After establishing the specificity of EAb, the site of entry of the infectious HIV-1-antibody (Ab) complexes into cells will be defined by following the inhibitory effect of antibodies to: (a) the CD4 (T4) receptor for HIV-1; (b) Fc receptors; and (c) complement C3b receptors on alpha) the infectivity of HIV-1 Ab complexes and Beta) the uptake of gp120/gp41 in the absence and presence of EAb with defined epitope specificity.