A Linear Epitope in the N-Terminal Domain of CCR5 and Its Interaction with Antibody.
A Linear Epitope in the N-Terminal Domain of CCR5 and Its Interaction with Antibody.
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DOI：
10.1371/journal.pone.0128381
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chayen N
中科院分区：
文献类型：
--
作者：
Chain B;Arnold J;Akthar S;Brandt M;Davis D;Noursadeghi M;Lapp T;Ji C;Sankuratri S;Zhang Y;Govada L;Saridakis E;Chayen N
CCR 5受体在几个关键的生理和病理过程中发挥作用，是重要的治疗靶点。通过被动或主动免疫抑制CCR 5轴提供了一种非常有选择性的干预策略。在这项研究中，我们定义了一个新的线性表位内的细胞外结构域的CCR 5识别的两个独立产生的单克隆抗体。当与破伤风类毒素辅助T细胞表位共线施用时，编码线性表位的短肽可以诱导识别完整受体的抗体。单克隆抗体RoAb 13显示出以中等至高亲和力（分别为6x10^8和1.2x107 M-1）结合细胞和肽，并且通过在位置10和14处的酪氨酸的硫酸化增强与肽的结合。RoAb 13以前已被证明可以阻断HIV感染，也可以阻断单核细胞响应于CCR 5结合趋化因子和炎性巨噬细胞条件培养基的迁移。RoAb 13的Fab片段已经结晶，并且抗体的结构报道为2.1埃分辨率。
The CCR5 receptor plays a role in several key physiological and pathological processes and is an important therapeutic target. Inhibition of the CCR5 axis by passive or active immunisation offers one very selective strategy for intervention. In this study we define a new linear epitope within the extracellular domain of CCR5 recognised by two independently produced monoclonal antibodies. A short peptide encoding the linear epitope can induce antibodies which recognise the intact receptor when administered colinear with a tetanus toxoid helper T cell epitope. The monoclonal antibody RoAb 13 is shown to bind to both cells and peptide with moderate to high affinity (6x10^8 and 1.2x107 M-1 respectively), and binding to the peptide is enhanced by sulfation of tyrosines at positions 10 and 14. RoAb13, which has previously been shown to block HIV infection, also blocks migration of monocytes in response to CCR5 binding chemokines and to inflammatory macrophage conditioned medium. A Fab fragment of RoAb13 has been crystallised and a structure of the antibody is reported to 2.1 angstrom resolution.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.5
作者：
Chain BM;Noursadeghi M;Gardener M;Tsang J;Wright E
通讯作者：
Wright E
影响因子：
5.4
作者：
Khurana, S;Kennedy, M;Golding, H
通讯作者：
Golding, H
影响因子：
56.9
作者：
LOH, EY;ELLIOTT, JF;DAVIS, MM
通讯作者：
DAVIS, MM