Evolution of the CD4 family: Teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3
Evolution of the CD4 family: Teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3
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DOI：
10.4049/jimmunol.177.6.3939
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Hansen, John D.
中科院分区：
文献类型：
--
作者：
Laing, Kerry J.;Zou, Jun J.;Hansen, John D.
T细胞辅受体CD4是一种跨膜糖蛋白，属于免疫球蛋白超家族，对细胞免疫是必不可少的。在虹鲑鱼中发现了两种不同的基因，它们与哺乳动物的CD4相似。一个(鲑鱼CD4)编码四个细胞外Ig结构域，使人想起哺乳动物的CD4，而另一个(CD4REL)编码两个Ig结构域。氨基酸序列中的结构基序表明，CD4REL的两个Ig结构域重复产生了CD4的四个结构域分子及其相关基因-淋巴细胞激活基因-3。在这里，我们提出的证据表明，鲑鱼中的这两个分子都与哺乳动物的CD4同源，硬骨鱼编码一个额外的CD4家族成员，淋巴细胞激活基因-3，这是激活的T细胞的标志。其他硬骨鱼和非鱼类基因组中相似基因的同线关系为脊椎动物中可能的CD4相关分子的进化提供了证据，CD4REL可能代表了鱼类的原始形式。这两个基因在胸腺和脾中的表达最高，并且这些基因的mRNA表达仅限于表面的IgM(-)淋巴细胞。与T细胞功能的作用一致。最后，CD4和CD4REL的胞内区都具有典型的CXC基序，参与了CD4与p56LCK的相互作用，这意味着所有脊椎动物都存在类似的CD4(+)T细胞激活机制。因此，我们的结果提出了关于低等脊椎动物T细胞发育和功能的新问题，这些问题不能用现有的哺乳动物模型来回答，因此，对于理解膝节体细胞介导免疫的进化具有重要意义。
The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig superfamily and is essential for cell-mediated immunity. Two different,genes were identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes four extracellular Ig domains reminiscent of mammalian CD4, whereas the other (CD4REL) codes for two Ig domains. Structural motifs within the amino acid sequences suggest that the two Ig domains of CD4REL duplicated to generate the four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3. Here we present evidence that both of these molecules in trout are homologous to mammalian CD4 and that teleosts encode an additional CD4 family member, lymphocyte activation gene-3, which is a marker for activated T cells. The syntenic relationships of similar genes in other teleost and non-fish genomes provide evidence for the likely evolution of CD4-related molecules in vertebrates, with CD4REL likely representing the primordial form in fish. Expression of both CD4 genes is highest in the thymus and spleen, and mRNA expression of these genes is limited to surface IgM(-) lymphocytes. consistent with a role for T cell functionality. Finally, the intracellular regions of both CD4 and CD4REL possess the canonical CXC motif involved in the interaction of CD4 with p56LCK, implying that similar mechanisms for CD4(+) T cell activation are present in all vertebrates. Our results therefore raise new questions about T cell development and functionality in lower vertebrates that cannot be answered by current mammalian models and, thus, is of fundamental importance for understanding the evolution of cell-mediated immunity in gnathosomes.