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Characterization of antibodies directed against fusion active core in gp41

针对 gp41 融合活性核心的抗体的表征

基本信息

批准号：
10670946
负责人：
HATTORI Toshio
金额：
$ 2.05万
依托单位：
TOHOKU UNIVERSITY (1999)Kyoto University (1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670946/
关键词：
HIV gp41 peptide DP178 fusion epitope fusion antibody

项目摘要

We asked whether the antibodies against two distinct extracellular _-helical regions of gp41 (DP107 and DP178) of human immunodeficiency virus type 1 have any relevance to clinical progressions. Anti-DP107 titers steadily declined as the disease progress. The decrease was statistically associated with the increase of vital load or the decrease of T cell numbers but not with the changes of B or NK cell numbers. In contrast, the antibodies against DP178 and gp41 remained elevated during the entire clinical course. A mixture of two peptides from gp41 (N36 and C34) forms an _-helical structure that is thought to represent the fusion active core of gp41. A human monoclonal anti-gp41 antibody (mAb 98-6), generated from the cells of an infected individual reacted poorly with C34, but binding was strongly enhanced when N36 was added, indicating that the mAb reacts with a conformational epitope present in the fusion active core structure formed by the interaction of peptides N36 and C34. The epitope recognized by mAb 98-6 was found in virions on oligomeric forms of gp41 (dimers, trimers and tetramers). On infected cells the epitope was present as oligomers of gp41, as monomers of gp41, and as part of the envelope polyprotein gp160. In infected cells, the epitope was present as part of both monomeric gp41 and gp160. These studies demonstrate that infected humans can respond to the fusion active form of gp41 and that the anti-gp41 mAb studied here recognizes a conformational epitope formed by the interaction of two regions of gp41, which form an _-helical bundle. This epitope is found on several forms of gp41 as they occur in virions, on the surface of infected cells, and in infected cells.

我们询问针对人类免疫缺陷病毒1型gp 41的两个不同胞外螺旋区（DP 107和DP 178）的抗体是否与临床进展有任何相关性。随着疾病的进展，抗DP 107滴度稳步下降。这种下降与生命负荷的增加或T细胞数量的减少有统计学相关性，但与B或NK细胞数量的变化无关。相反，在整个临床过程中，针对DP 178和gp 41的抗体保持升高。来自gp 41的两种肽（N36和C34）的混合物形成_螺旋结构，其被认为代表gp 41的融合活性核心。由感染个体的细胞产生的人单克隆抗gp 41抗体（mAb 98-6）与C34反应较差，但当加入N36时结合强烈增强，表明mAb与存在于由肽N36和C34的相互作用形成的融合活性核心结构中的构象表位反应。在gp 41的寡聚体形式（二聚体、三聚体和四聚体）上的病毒体中发现了mAb 98-6识别的表位。在感染的细胞上，表位以gp 41的寡聚体、gp 41的单体和包膜多蛋白gp 160的一部分存在。在感染的细胞中，表位作为单体gp 41和gp 160的一部分存在。这些研究表明，受感染的人可以响应gp 41的融合活性形式，并且这里研究的抗gp 41 mAb识别由gp 41的两个区域相互作用形成的构象表位，其形成螺旋束。该表位存在于几种形式的gp 41上，因为它们存在于病毒体、感染细胞的表面和感染细胞中。