Tokyo Research Laboratory, Tosoh Corporation, Ayase, Kanagawa, 252-1123, Japan.
Mol Immunol. 2013 Jul;54(3-4):403-7. doi: 10.1016/j.molimm.2013.01.007. Epub 2013 Feb 9.
Human FcγRI is a high affinity receptor for the Fc portion of human immunoglobulin G (IgG), and has extracellular, transmembrane and cytoplasmic regions. The extracellular region of human FcγRI, which is the part that interacts with human IgG, is comprised of three immunoglobulin-like domains. Unlike low affinity Fcγ receptors (FcγRII and FcγRIII), FcγRI has a unique third extracellular domain (D3). This study investigated the contribution of D3 to the binding between recombinant human FcγRI (rhFcγRI) and human IgG. The three extracellular domains and the first and second extracellular domains of human FcγRI were expressed by Escherichia coli as rhFcγRI and rhFcγRI-D1D2, respectively. The binding specificity of rhFcγRI-D1D2 to human IgG subclasses was the same as that of rhFcγRI. From surface plasmon resonance analysis, the binding affinity of rhFcγRI-D1D2 for human IgG1/κ was high (the equilibrium dissociation constant: KD=8.04 × 10(-10)M), but slightly lower than that of rhFcγRI (KD=2.59 × 10(-10)M). While the association of rhFcγRI-D1D2 with human IgG1/κ was same as that of rhFcγRI, the dissociation of rhFcγRI-D1D2 was faster than that of rhFcγRI. From these results, D3 of rhFcγRI would not contribute directly to the binding specificity and association of rhFcγRI, but to the holding bound human IgG.
人 FcγRI 是人类免疫球蛋白 G（IgG）Fc 部分的高亲和力受体，具有细胞外、跨膜和细胞质区域。人 FcγRI 的细胞外区域，即与人 IgG 相互作用的部分，由三个免疫球蛋白样结构域组成。与低亲和力 Fcγ 受体（FcγRII 和 FcγRIII）不同，FcγRI 具有独特的第三个细胞外结构域（D3）。本研究探讨了 D3 对重组人 FcγRI（rhFcγRI）与人 IgG 之间结合的贡献。三个细胞外结构域和人 FcγRI 的第一和第二细胞外结构域分别由大肠杆菌表达为 rhFcγRI 和 rhFcγRI-D1D2。rhFcγRI-D1D2 与人 IgG 亚类的结合特异性与 rhFcγRI 相同。表面等离子体共振分析表明，rhFcγRI-D1D2 与人 IgG1/κ 的结合亲和力很高（平衡解离常数：KD=8.04×10(-10)M），但略低于 rhFcγRI（KD=2.59×10(-10)M）。虽然 rhFcγRI-D1D2 与人 IgG1/κ 的结合与 rhFcγRI 相同，但 rhFcγRI-D1D2 的解离速度快于 rhFcγRI。从这些结果来看，rhFcγRI 的 D3 不会直接影响 rhFcγRI 的结合特异性和结合，而是影响结合的人 IgG。
