Structural analysis of B-cell epitopes in antibody:protein complexes.
Structural analysis of B-cell epitopes in antibody:protein complexes.
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DOI：
10.1016/j.molimm.2012.06.001
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发表时间：
2013-01
影响因子：
3.6
通讯作者：
Lund O
中科院分区：
文献类型：
--
作者：
Kringelum JV;Nielsen M;Padkjær SB;Lund O
抗原与抗体的结合是针对外来分子的免疫反应中的关键事件之一，也是包括疫苗和免疫治疗在内的几种生物医学应用的关键要素。为了开发这类应用，抗体结合部位(B细胞表位)的鉴定是必不可少的。然而，试验性表位测绘的成本很高，计算机辅助方法总体上确实有中等的性能。表现平平的一个主要原因是对表位特征的理解不全面。为了填补这一空白，我们在这里开发了一个新的框架，用于比较和叠加B细胞表位，并将其应用于107个不相似抗原的数据集：从PDB数据库中提取的抗体结构。在目前的框架下，我们能够将一般的B细胞表位描述为一个扁平的、长方形的、椭圆形的体积，由中心的主要疏水氨基酸组成，两侧是带电残基。平均表位由~15个残基组成，一个由5个或更多残基组成的线性延伸构成了表位大小的一半以上。此外，表位区域主要被限制在抗体尖端上方的平面，在该平面中，表位相对于轻到重链抗体方向以−30到60度角定向。与之前的发现相反，我们没有发现抗原表位中的氨基酸组成与抗原表面同样暴露的部分的组成之间存在明显的偏差。我们的结果，结合以前的发现，给出了B细胞表位的详细图景，可以用于开发改进的B细胞预测方法。
The binding of antigens to antibodies is one of the key events in an immune response against foreign molecules and is a critical element of several biomedical applications including vaccines and immunotherapeutics. For development of such applications, the identification of antibody binding sites (B-cell epitopes) is essential. However experimental epitope mapping is highly cost-intensive and computer-aided methods do in general have moderate performance. One major reason for this moderate performance is an incomplete understanding of what characterizes an epitope. To fill this gap, we here developed a novel framework for comparing and superimposing B-cell epitopes and applied it on a dataset of 107 non-similar antigen:antibody structures extracted from the PDB database. With the presented framework, we were able to describe the general B-cell epitope as a flat, oblong, oval shaped volume consisting of predominantly hydrophobic amino acids in the center flanked by charged residues. The average epitope was found to be made up of ~15 residues with one linear stretch of 5 or more residues constituting more than half of the epitope size. Furthermore, the epitope area is predominantly constrained to a plane above the antibody tip, in which the epitope is orientated in a −30 to 60 degree angle relative to the light to heavy chain antibody direction. Contrary to previously findings, we did not find a significant deviation between the amino acid composition in epitopes and the composition of equally exposed parts of the antigen surface. Our results, in combination with previously findings, give a detailed picture of the B-cell epitope that may be used in development of improved B-cell prediction methods.
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DOI：
10.1038/nsb930
发表时间：
2003-06-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Li, YL;Li, HM;Mariuzza, RA
通讯作者：
Mariuzza, RA
影响因子：
3.6
作者：
Lollier V;Denery-Papini S;Larré C;Tessier D
通讯作者：
Tessier D
DOI：
10.2165/00063030-200721030-00002
发表时间：
2007
期刊：
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
影响因子：
--
作者：
Gershoni JM;Roitburd-Berman A;Siman-Tov DD;Tarnovitski Freund N;Weiss Y
通讯作者：
Weiss Y
影响因子：
3
作者：
Liang S;Zheng D;Standley DM;Yao B;Zacharias M;Zhang C
通讯作者：
Zhang C
影响因子：
7.8
作者：
Irving MB;Pan O;Scott JK
通讯作者：
Scott JK