Antigenicity and immunogenicity of the HIV-1 gp41 epitope ELDKWA inserted into permissive sites of the MalE protein
Antigenicity and immunogenicity of the HIV-1 gp41 epitope ELDKWA inserted into permissive sites of the MalE protein
复制标题
DOI：
10.1016/s0264-410x(00)00267-x
复制
发表时间：
2000-11-22
期刊：
影响因子：
5.5
通讯作者：
Leclerc, C
中科院分区：
文献类型：
--
作者：
Coëffier, E;Clément, JM;Leclerc, C
HIV-1 gp 41的高度保守氨基酸序列ELDKWA已被插入大肠杆菌MalE蛋白中，该蛋白已被证明是将外源表位呈递给免疫系统的适当载体。我们首先研究了MalE的8个不同的允许位点是否能够耐受编码该表位的7-50个残基的插入。其次，使用BIAcore（R）技术从单克隆抗体2F 5结合分析估计插入MalE蛋白中的表位的抗原性，并测量其在小鼠中的免疫原性，作为杂合蛋白引发针对含有该表位的合成肽的抗体的能力。该研究揭示了插入表位的抗原性与其免疫原性之间的良好相关性。增加插入表位的长度以及插入该表位的多拷贝增加了其抗原性和免疫原性。然而，测试的MalE杂合蛋白均未诱导抗HIV-1中和抗体。这项研究强烈表明，2F 5表位诱导中和抗体的能力取决于其所处的分子环境。(C)2000爱思唯尔科技有限公司版权所有。
The highly conserved amino acid sequence ELDKWA of HIV-1 gp41 has been inserted into Escherichia coli MalE protein which had been shown to be an adequate carrier to present foreign epitopes to the immune system. We first investigated whether eight different permissive sites of MalE are able to tolerate an insertion of 7-50 residues encoding this epitope. Secondly, antigenicity:of the epitope inserted in MalE protein was estimated from monoclonal antibody 2F5 binding analysis using the BIAcore(R) technology and its immunogenicity in mice was measured as the ability of hybrid proteins to elicit antibodies against a synthetic peptide containing this epitope. This study revealed a good correlation between the antigenicity of the inserted epitope and its immunogenicity. Increasing the length of the inserted epitope, as well as inserting multicopies of this epitope increased both its antigenicity and immunogenicity. However, none of the MalE hybrid proteins tested induced anti-HIV-1 neutralizing antibodies. This study strongly suggests that the capacity of the 2F5 epitope to induce neutralizing antibodies depends on the molecular context in which it is presented. (C) 2000 Elsevier Science Ltd. All rights reserved.