Wright Jill F, Guo Yongjing, Quazi Amira, Luxenberg Deborah P, Bennett Frann, Ross John F, Qiu Yongchang, Whitters Matthew J, Tomkinson Kathleen N, Dunussi-Joannopoulos Kyri, Carreno Beatriz M, Collins Mary, Wolfman Neil M
Department of Inflammation, Wyeth Research, Cambridge, Massachusetts 02140, USA.
J Biol Chem. 2007 May 4;282(18):13447-55. doi: 10.1074/jbc.M700499200. Epub 2007 Mar 13.
IL-17F and IL-17A are members of the IL-17 pro-inflammatory cytokine family. IL-17A has been implicated in the pathogenesis of autoimmune diseases. IL-17F is a disulfide-linked dimer that contains a cysteine-knot motif. We hypothesized that IL-17F and IL-17A could form a heterodimer due to their sequence homology and overlapping pattern of expression. We evaluated the structure of recombinant IL-17F and IL-17A proteins, as well as that of natural IL-17F and IL-17A derived from activated human CD4+ T cells, by enzyme-linked immunosorbent assay, immunoprecipitation followed by Western blotting, and mass spectrometry. We find that both IL-17F and IL-17A can form both homodimeric and heterodimeric proteins when expressed in a recombinant system, and that all forms of the recombinant proteins have in vitro functional activity. Furthermore, we find that in addition to the homodimers of IL-17F and IL-17A, activated human CD4+ T cells also produce the IL-17F/IL-17A heterodimer. These data suggest that the IL-17F/IL-17A heterodimer may contribute to the T cell-mediated immune responses.
白细胞介素-17F（IL-17F）和白细胞介素-17A（IL-17A）是促炎细胞因子白细胞介素-17家族的成员。IL-17A与自身免疫性疾病的发病机制有关。IL-17F是一种含二硫键的二聚体，包含一个半胱氨酸结基序。我们推测，由于IL-17F和IL-17A的序列同源性和重叠的表达模式，它们可能形成异源二聚体。我们通过酶联免疫吸附测定、免疫沉淀后进行蛋白质印迹分析以及质谱分析，评估了重组IL-17F和IL-17A蛋白的结构，以及源自活化的人CD4+T细胞的天然IL-17F和IL-17A的结构。我们发现，当在重组系统中表达时，IL-17F和IL-17A都能形成同源二聚体和异源二聚体蛋白，并且所有形式的重组蛋白都具有体外功能活性。此外，我们发现，除了IL-17F和IL-17A的同源二聚体外，活化的人CD4+T细胞还产生IL-17F/IL-17A异源二聚体。这些数据表明，IL-17F/IL-17A异源二聚体可能有助于T细胞介导的免疫反应。
