Alder Matthew N, Rogozin Igor B, Iyer Lakshminarayan M, Glazko Galina V, Cooper Max D, Pancer Zeev
Howard Hughes Medical Institute, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Science. 2005 Dec 23;310(5756):1970-3. doi: 10.1126/science.1119420.
Instead of the immunoglobulin-type antigen receptors of jawed vertebrates, jawless fish have variable lymphocyte receptors (VLRs), which consist of leucine-rich repeat (LRR) modules. Somatic diversification of the VLR gene is shown here to occur through a multistep assembly of LRR modules randomly selected from a large bank of flanking cassettes. The predicted concave surface of the VLR is lined with hypervariable positively selected residues, and computational analysis suggests a repertoire of about 10(14) unique receptors. Lamprey immunized with anthrax spores responded with the production of soluble antigen-specific VLRs. These findings reveal that two strikingly different modes of antigen recognition through rearranged lymphocyte receptors have evolved in the jawless and jawed vertebrates.
与有颌脊椎动物的免疫球蛋白型抗原受体不同，无颌鱼类具有可变淋巴细胞受体（VLR），其由富含亮氨酸的重复序列（LRR）模块组成。本文显示，VLR基因的体细胞多样化是通过从大量侧翼盒式结构中随机选择的LRR模块进行多步组装而发生的。VLR预测的凹面排列着高变的正选择残基，计算分析表明约有10¹⁴种独特受体。用炭疽芽孢免疫的七鳃鳗会产生可溶性抗原特异性VLR。这些发现揭示，在无颌和有颌脊椎动物中，通过重排的淋巴细胞受体进行抗原识别的两种截然不同的模式已经进化出来。
