Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, Georgia 30322, USA.
Nature. 2013 Sep 19;501(7467):435-8. doi: 10.1038/nature12467. Epub 2013 Aug 11.
Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems. Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily. Cyclostomes, the lampreys and hagfish, instead use leucine-rich repeat proteins to construct variable lymphocyte receptors (VLRs), two types of which, VLRA and VLRB, are reciprocally expressed by lymphocytes resembling gnathostome T and B cells. Here we define another lineage of T-cell-like lymphocytes that express the recently identified VLRC receptors. Both VLRC(+) and VLRA(+) lymphocytes express orthologues of genes that gnathostome γδ and αβ T cells use for their differentiation, undergo VLRC and VLRA assembly and repertoire diversification in the 'thymoid' gill region, and express their VLRs solely as cell-surface proteins. Our findings suggest that the genetic programmes for two primordial T-cell lineages and a prototypic B-cell lineage were already present in the last common vertebrate ancestor approximately 500 million years ago. We propose that functional specialization of distinct T-cell-like lineages was an ancient feature of a primordial immune system.
有颌类（颌口类）和无颌类（圆口类）具有不同的适应性免疫系统。颌口类使用属于免疫球蛋白超家族的 T 细胞和 B 细胞抗原受体。而圆口类，即七鳃鳗和盲鳗，则使用富含亮氨酸的重复蛋白来构建可变淋巴细胞受体（VLR），其中两种类型，VLR-A 和 VLR-B，由类似于颌口类 T 和 B 细胞的淋巴细胞相互表达。在这里，我们定义了另一种 T 细胞样淋巴细胞谱系，其表达最近鉴定的 VLR-C 受体。VLRC(+)和 VLRA(+)淋巴细胞均表达颌口类 γδ 和 αβ T 细胞用于其分化的基因的同源物，在“胸腺”鳃区进行 VLRC 和 VLRA 组装和库多样化，并仅将其 VLR 作为细胞表面蛋白表达。我们的发现表明，两种原始 T 细胞谱系和一种原始 B 细胞谱系的遗传程序大约在 5 亿年前的最后一个共同脊椎动物祖先中就已经存在。我们提出，不同 T 细胞样谱系的功能特化是原始免疫系统的一个古老特征。
