Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey
Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey
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DOI：
10.1038/nature02740
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发表时间：
2004-07-08
期刊：
影响因子：
64.8
通讯作者：
Cooper, MD
中科院分区：
文献类型：
--
作者：
Pancer, Z;Amemiya, CT;Cooper, MD
虽然无颌脊椎动物显然能够适应性免疫反应，但尚未发现它们具有所有有颌脊椎动物共有的重组抗原受体。我们在七鳃鳗中寻找适应性免疫的系统发育根源，却发现了一种新型的可变淋巴细胞受体（VLRs），由夹在氨基和羧基末端LRR之间的高度多样的富含亮氨酸的重复序列（LRR）组成。不变的茎区通过糖基-磷脂酰-肌醇锚将VLRs束缚在细胞表面。为了产生预期免疫系统所需的多样性的重排的VLR基因，单个七鳃鳗VLR基因座包含大量不同的LRR盒，可用于插入不完整的种系VLR基因。单个淋巴细胞以单等位基因方式表达独特重排的VLR基因。不同的进化策略，从而产生高度多样化的淋巴细胞受体，通过重排LRR模块无颌鱼（无颌鱼）和gnathostomes（有颌脊椎动物）的免疫球蛋白基因片段。
Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).