Mapping the immune response to the outer domain of a human immunodeficiency virus-1 clade C gp120.
Mapping the immune response to the outer domain of a human immunodeficiency virus-1 clade C gp120.
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DOI：
10.1099/vir.0.2008/003491-0
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Jones IM
中科院分区：
文献类型：
--
作者：
Chen H;Xu X;Lin HH;Chen SH;Forsman A;Aasa-Chapman M;Jones IM
人类免疫缺陷病毒(HIV)-1 gp120的外区(OD)代表了对HIV感染的有益免疫反应的一个有吸引力的(如果困难的)靶标。与整个gp120不同，OD在结构上是稳定的，包含与初级和次级细胞受体相互作用的表面。主要的毒株特异性中和靶点V3环位于OD内，两个交叉反应的中和单抗B12和2G12的表位也在OD内，以及一些抑制性凝集素的接触部位。OD的免疫原性很差，至少在完整的gp120的背景下是如此，但有目的的OD免疫可以导致大量的抗体反应。在这里，我们映射免疫后产生的抗体分支C OD。与已发表的分支BOD数据相比，对完整分支C OD的大多数多克隆反应是针对V3环；环的删除大大降低了免疫原性。当环状序列取代2F5的表位时，就产生了对该表位的多克隆反应。针对C分支OD的一组单抗鉴定出两个与环反应的单抗，它们对C分支分离株有中和作用，但对B分离株没有中和作用。其他单抗可识别OD中线性表位和构象表位。我们的结论是，对于完整的gp120，V3免疫优势是OD免疫原的一种特性，其反应可以是中和的，它可以被用来呈现其他表位。
The outer domain (OD) of human immunodeficiency virus (HIV)-1 gp120 represents an attractive, if difficult, target for a beneficial immune response to HIV infection. Unlike the entire gp120, the OD is structurally stable and contains the surfaces that interact with both the primary and secondary cellular receptors. The primary strain-specific neutralizing target, the V3 loop, lies within the OD, as do epitopes for two cross-reactive neutralizing monoclonal antibodies (mAbs), b12 and 2G12, and the contact sites for a number of inhibitory lectins. The OD is poorly immunogenic, at least in the context of complete gp120, but purposeful OD immunization can lead to a substantial antibody response. Here, we map the antibody generated following immunization with a clade C OD. In contrast to published data for the clade B OD, the majority of the polyclonal response to the complete clade C OD is to the V3 loop; deletion of the loop substantially reduces immunogenicity. When the loop sequence was substituted for the epitope for 2F5, a well-characterized human cross-neutralizing mAb, a polyclonal response to the epitope was generated. A panel of mAbs against the clade C OD identified two mAbs that reacted with the loop and were neutralizing for clade C but not B isolates. Other mAbs recognized both linear and conformational epitopes in the OD. We conclude that, as for complete gp120, V3 immunodominance is a property of OD immunogens, that the responses can be neutralizing and that it could be exploited for the presentation of other epitopes.
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