Nelson Mandela Metropolitan University, Port Elizabeth, South Africa.
Cell Immunol. 2011;271(2):371-8. doi: 10.1016/j.cellimm.2011.08.003. Epub 2011 Aug 12.
IgE, responsible for type I hypersensitivities, is regulated by interactions between its receptor, CD23, and co-receptor CD21. To examine comparative binding of recombinant human CD21 SCR 1-2 and native human IgE to CD23 plus the effect of CD23 on IgE production, we engineered recombinant soluble human CD23 fragments; (1) derCD23, (2) sCD23 and (3) exCD23, formed in vivo by proteolysis. SPR analysis revealed a progressive increment in affinity of soluble fragments for IgE, upon increasing length of CD23 "stalk" domain, exCD23>sCD23>derCD23. Soluble CD23 fragments and their oligomeric state are shown to fine-tune the immune response. Oligomers appear more important in enhancing IgE synthesis and monomers lacking the tail residues fail to bind CD21 yet bind membrane IgE and down-regulate IgE synthesis. Co-ligation of membrane IgE and CD21 through soluble CD23 monomers is disturbed. This study supports anti-allergic therapies involving stabilizing membrane CD23, or preventing shedding of soluble CD23.
IgE 负责 I 型超敏反应,其受体 CD23 和共受体 CD21 的相互作用受其调节。为了研究重组人 CD21 SCR 1-2 和天然人 IgE 与 CD23 的比较结合以及 CD23 对 IgE 产生的影响,我们构建了重组可溶性人 CD23 片段;(1)derCD23,(2)sCD23 和(3)exCD23,由体内蛋白酶解形成。SPR 分析显示,可溶性片段与 IgE 的亲和力随着 CD23“茎”结构域长度的增加而逐渐增加,exCD23>sCD23>derCD23。可溶性 CD23 片段及其寡聚状态被证明可以微调免疫反应。寡聚体似乎在增强 IgE 合成方面更为重要,而缺乏尾部残基的单体无法结合 CD21,但可结合膜 IgE 并下调 IgE 合成。通过可溶性 CD23 单体对膜 IgE 和 CD21 的共交联受到干扰。这项研究支持涉及稳定膜 CD23 或防止可溶性 CD23 脱落的抗过敏治疗。