The binding of soluble recombinant human Fcγ receptor I for human immunoglobulin G is conferred by its first and second extracellular domains.

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.