Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.
Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
Immunol Rev. 2015 Nov;268(1):222-35. doi: 10.1111/imr.12340.
Immunoglobulin E (IgE) is well known for its role in allergic disease, the manifestations of which are mediated through its two Fc receptors, FcεRI and CD23 (FcεRII). IgE and its interactions with these receptors are therefore potential targets for therapeutic intervention, and exciting progress has been made in this direction. Furthermore, recent structural studies of IgE-Fc, the two receptors, and of their complexes, have revealed a remarkable degree of plasticity at the IgE-CD23 interface and an even more remarkable degree of dynamic flexibility within the IgE molecule. Indeed, there is allosteric communication between the two receptor-binding sites, which we now know are located at some distance from each other in IgE-Fc (at opposite ends of the Cε3 domain). The conformational changes associated with FcεRI and CD23 binding to IgE-Fc ensure that their interactions are mutually incompatible, and it may be that this functional imperative has driven IgE to evolve such a dynamic structure. Appreciation of these new structural data has revised our view of IgE structure, shed light on the co-evolution of antibodies and their receptors, and may open up new therapeutic opportunities.
免疫球蛋白 E（IgE）因其在过敏疾病中的作用而广为人知，其表现通过其两个 Fc 受体，FcεRI 和 CD23（FcεRII）介导。因此，IgE 及其与这些受体的相互作用是治疗干预的潜在目标，在这方面已经取得了令人兴奋的进展。此外，最近对 IgE-Fc、两个受体及其复合物的结构研究揭示了 IgE-CD23 界面的显著可塑性，以及 IgE 分子内更显著的动态灵活性。事实上，两个受体结合位点之间存在变构通讯，我们现在知道它们在 IgE-Fc 中彼此相距很远（在 Cε3 结构域的两端）。与 FcεRI 和 CD23 结合到 IgE-Fc 相关的构象变化确保了它们的相互作用是相互排斥的，可能正是这种功能要求促使 IgE 进化出这样一种动态结构。对这些新结构数据的理解修正了我们对 IgE 结构的看法，阐明了抗体及其受体的共同进化，并可能开辟新的治疗机会。
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