Somatic hypermutation of TCR γ V genes in the sandbar shark
Somatic hypermutation of TCR γ V genes in the sandbar shark
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DOI：
10.1016/j.dci.2011.08.018
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发表时间：
2012-05-01
影响因子：
2.9
通讯作者：
Schluter, Samuel F.
中科院分区：
文献类型：
--
作者：
Chen, Hao;Bernstein, Harris;Schluter, Samuel F.
在最近的出版物中，我们证明了体细胞高突变发生在V区的TCR γ基因的沙洲鲨（Carcharhinus铅）。我们假设，类似的机制是用来产生体细胞突变的免疫球蛋白和TCR γ基因的鲨鱼。发生两种不同的突变模式，单核苷酸突变（点突变）和包含2-5个连续碱基的突变（串联突变）。我们的数据表明，点突变发生的机制类似于哺乳动物免疫球蛋白基因的体细胞超突变，而串联突变可能产生的易错的DNA聚合酶与末端脱氧核苷酸转移酶（TdT）样活性。鲨鱼热点图案相同的高等脊椎动物被确定。我们证实，在鲨鱼和高等脊椎动物的免疫球蛋白，非常显着的AID活动的经典DGYW/WRCH基序的靶向发生在体细胞超突变的沙洲鲨TCR γ V基因。我们的分析表明，鲨鱼TCR γ V区的体细胞突变的目的是在γ/δ受体中产生更多样化的库，而不是具有更高亲和力的受体。(C)2011爱思唯尔有限公司版权所有。
In a recent publication we demonstrated that somatic hypermutation occurs in the V region of the TCR gamma gene of the sandbar shark (Carcharhinus plumbous). We hypothesize that similar mechanisms are used to generate somatic mutations in both immunoglobulin and TCR gamma genes of the sharks. Two distinct patterns of mutation occur, single nucleotide mutations (point mutations) and mutations comprising 2-5 consecutive bases (tandem mutations). Our data indicates that point mutations occur by a mechanism similar to that of somatic hypermutation in immunoglobulin genes of mammals, whereas tandem mutations may be generated by an error-prone DNA polymerase with terminal deoxynucleotidyl transferase (TdT)-like activity. Shark hotspot motifs identical to those of higher vertebrates were identified. We confirm that, as in immunoglobulin of sharks and higher vertebrates, highly significant targeting of AID activity to the classical DGYW/WRCH motif occurs in somatic hypermutation of sandbar shark TCR gamma V genes. Our analysis suggests that the purpose of somatic mutations in shark TCR gamma V-regions is to generate a more diverse repertoire in gamma/delta receptors, rather than receptors with higher affinity. (C) 2011 Elsevier Ltd. All rights reserved.