《Nature》：免疫系统的演化起源
http://www.100md.com
2004年7月8日
所有植物和动物都利用先天受体来识别病原体。脊椎动物在先天受体基础上又增添了一组更为多样的受体，即我们人类与鲨鱼和其他有颚脊椎动物共有的“适应性” 免疫系统。以七鳃鳗(见本期封面照片)为代表的无颚脊椎动物可能含有了解我们人类免疫系统演化起源的关键线索。它们有一种适应性免疫响应，但不是我们在有颚脊椎动物中看到的重组抗原受体。对七鳃鳗所含有的脊椎动物免疫系统的原始元素所做的新的搜索工作，在淋巴细胞一样的细胞上发现了新型可变受体，它们利用一种不寻常的基因重排过程来产生受体多样性。这表明，我们的脊椎动物祖先曾尝试过不止一种办法来形成一种适应性免疫系统。
Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey
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).
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Figure 3 Graphic representation of protein divergence among 112 VLR diversity regions PCR amplified from 13 individual lampreys. Animal and clone numbers are indicated in red for immunostimulated (N = 27) and green for unstimulated (N = 41) larvae. Asterisks indicate VLRs derived from single lymphocytes (N = 12), including two VLRs from one isolate (9.16S, 9.16L); clones derived from a control ten-cell pool are denoted 10C (N = 4). Mature VLR sequences derived from genomic DNA are in blue (N = 28; blood, animal 10, 12; carcass, animal 11, 13). The mean diversity is 0.36
0.03 ( s.d.), ranging from 0.28 to 0.54 within the groups of sequences from 13 individuals. Scale bar indicates per cent amino acid divergence.
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Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey
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).
, http://www.100md.com
Figure 3 Graphic representation of protein divergence among 112 VLR diversity regions PCR amplified from 13 individual lampreys. Animal and clone numbers are indicated in red for immunostimulated (N = 27) and green for unstimulated (N = 41) larvae. Asterisks indicate VLRs derived from single lymphocytes (N = 12), including two VLRs from one isolate (9.16S, 9.16L); clones derived from a control ten-cell pool are denoted 10C (N = 4). Mature VLR sequences derived from genomic DNA are in blue (N = 28; blood, animal 10, 12; carcass, animal 11, 13). The mean diversity is 0.36
0.03 ( s.d.), ranging from 0.28 to 0.54 within the groups of sequences from 13 individuals. Scale bar indicates per cent amino acid divergence.全文下载：
点击浏览该文件, 百拇医药(生物谷)