The D1 domain of the CD4 co-receptor interacts with MHC class II during Helper CD4+ Th-cell activation and effector function in all gnathostomes but the sequence and structure of this region are not well conserved through phylogeny. Conversely, the proximal D4 domain of CD4 is the binding site of the cytokine IL-16 and is highly conserved, allowing for promiscuous binding of IL-16 to CD4 between disparate gnathostomes. We report here that recombinant human IL-16 (rhIL-16) bound to Xenopus lymphocytes to allow separation on a magnetic column. Incubation with rhIL-16 resulted in an increased expression of MHC class II mRNA by Xenopus CD8- cells more than by CD8+ cells. An in vivo assay demonstrated that rhIL-16 can recruit lymphocytes of Xenopus frogs. Our data suggest that a subset of Xenopus laevis lymphocytes express a CD4 homolog on their surface that is capable of binding IL-16. These results imply that CD4 most likely arose from a primordial cytokine receptor.

中文翻译：

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初步迹象表明重组人 IL-16 吸引和刺激两栖动物的淋巴细胞，非洲爪蟾暗示 CD4 作为细胞因子受体的祖先作用

CD4 共受体的 D1 域在辅助 CD4+ Th 细胞激活和所有有颚类中的效应子功能期间与 MHC II 类相互作用，但该区域的序列和结构在系统发育中并未得到很好的保守。相反，CD4 的近端 D4 结构域是细胞因子 IL-16 的结合位点，并且高度保守，允许 IL-16 在不同的有颚体之间混杂结合到 CD4。我们在此报告重组人 IL-16 (rhIL-16) 与非洲爪蟾淋巴细胞结合以允许在磁柱上分离。与rhIL-16 一起温育导致非洲爪蟾CD8-细胞的MHC II 类mRNA 的表达高于CD8+ 细胞。体内试验表明，rhIL-16 可以募集非洲爪蟾蛙的淋巴细胞。我们的数据表明爪蟾淋巴细胞的一个子集在其表面表达能够结合 IL-16 的 CD4 同系物。这些结果意味着 CD4 最有可能来自原始细胞因子受体。