The human low affinity Fc gamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties

Fc gamma receptors (Fc gamma Rs) are expressed on all immunologically activ e cells. They bind the Fe portion of IgG, thereby triggering a range of imm unological functions. We have used surface plasmon resonance to analyze the kinetic and thermodynamic properties of the interactions between the ectod omains of human low affinity Fc gamma Rs (Fc gamma RIIa, Fc gamma RIIb, and Fc gamma gamma RIIb-NA2) and IgG1 or the Fc fragment of IgG1. All three re ceptors bind Fc or IgG with similarly low affinities (K-D similar to0.6-2.5 muM) and fast kinetics, suggesting that Fc gammaR-mediated recognition of aggregated IgG and IgG-coated particles or cells is mechanistically similar to cell-cell recognition. Interestingly, the Fe receptors exhibit distinct thermodynamic properties. Whereas the binding of the Fc gamma RIIa and Fc gamma RIIb to Fe is driven by favorable entropic and enthalpic changes, the binding of Fc gamma RIII is characterized by highly unfavorable entropic c hanges. Although the structural bases for these differences remain to be de termined, they suggest that the molecular events coupled to the binding dif fer among the low affinity Fc gamma Rs.