Comparative analysis of human and mouse immunoglobulin variable heavy regions from IMGT/LIGM-DB with IMGT/HighV-QUEST.
Comparative analysis of human and mouse immunoglobulin variable heavy regions from IMGT/LIGM-DB with IMGT/HighV-QUEST.
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DOI：
10.1186/1742-4682-11-30
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发表时间：
2014-07-03
影响因子：
--
通讯作者：
Yao X
中科院分区：
文献类型：
--
作者：
Shi B;Ma L;He X;Wang X;Wang P;Zhou L;Yao X
免疫球蛋白（IG）互补决定区（CDR）包括VH CDR 1、VH CDR 2、VH CDR 3、VL CDR 1、VL CDR 2和VL CDR 3。其中，VH CDR 3在识别和结合抗原中起主导作用。三种主要机制参与VH库的形成：生殖系基因重排、连接多样性和体细胞超突变。人和小鼠中VH库的产生机制的特征具有相似性，而VH CDR 3氨基酸（AA）组成不同。以前的研究主要集中在人类和小鼠的生殖系基因重排和CDR 3 AA的组成和结构。然而，由于体细胞超突变和连接机制的分析AA的变化的数量一直被忽视。在此，我们分析了源自顶GT/LIGM-DB数据库的免疫球蛋白（IG）可变重链（VH）结构域的9，340个人和6，657个鼠独特的生产性序列，以了解VH CDR 3 AA组成在人和小鼠之间如何显著不同。通过顶GT/HighV-QUEST（http：//www.example.com）鉴定和分析这些序列，包括基因使用、由于体细胞超突变引起的AA变化的数量、VH CDR 3的AA长度分布、AA组成和连接多样性。www.imgt.org人和小鼠IG库的分析显示出显着差异。与小鼠相比，在人类中发现了更多数量的由于体细胞超突变和更丰富的N-区添加而引起的AA变化，这可能是导致VH CDR 3氨基酸组成差异的重要因素。这些发现是理解VH库的基准，并且可以用于表征免疫应答期间的VH库。该研究将允许对通过IMGT/HighV-QUEST（NGS库的参考门户）获得的高通量结果进行标准化比较。
Immunoglobulin (IG) complementarity determining region (CDR) includes VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3. Of these, VH CDR3 plays a dominant role in recognizing and binding antigens. Three major mechanisms are involved in the formation of the VH repertoire: germline gene rearrangement, junctional diversity and somatic hypermutation. Features of the generation mechanisms of VH repertoire in humans and mice share similarities while VH CDR3 amino acid (AA) composition differs. Previous studies have mainly focused on germline gene rearrangement and the composition and structure of the CDR3 AA in humans and mice. However the number of AA changes due to somatic hypermutation and analysis of the junctional mechanism have been ignored. Here we analyzed 9,340 human and 6,657 murine unique productive sequences of immunoglobulin (IG) variable heavy (VH) domains derived from IMGT/LIGM-DB database to understand how VH CDR3 AA compositions significantly differed between human and mouse. These sequences were identified and analyzed by IMGT/HighV-QUEST (http://www.imgt.org), including gene usage, number of AA changes due to somatic hypermutation, AA length distribution of VH CDR3, AA composition, and junctional diversity. Analyses of human and murine IG repertoires showed significant differences. A higher number of AA changes due to somatic hypermutation and more abundant N-region addition were found in human compared to mouse, which might be an important factor leading to differences in VH CDR3 amino acid composition. These findings are a benchmark for understanding VH repertoires and can be used to characterize the VH repertoire during immune responses. The study will allow standardized comparison for high throughput results obtained by IMGT/HighV-QUEST, the reference portal for NGS repertoire.
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影响因子：
--
作者：
Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
--
作者：
Giudicelli, Veronique;Brochet, Xavier;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
64.5
作者：
BEREK, C;BERGER, A;APEL, M
通讯作者：
APEL, M
影响因子：
14.9
作者：
Giudicelli, Veronique;Duroux, Patrice;Ginestoux, Chantal;Folch, Geraldine;Jabado-Michaloud, Joumana;Chaume, Denys;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
2.9
作者：
Lefranc, MP;Pommié, C;Lefranc, G
通讯作者：
Lefranc, G