Stoichiometry and Thermodynamics of the Interaction between the Fc Fragment of Human IgG₁ and Its Low-Affinity Receptor FcγRIII

IgG-Fc receptors, cell surface glycoproteins binding the Fc region of antibodies, play a crucial role in the immune system. To better understand the nature of the recognition process, we have examined the interaction between huIgG₁-Fc and a soluble fragment of huFcγRIII (sCD16). Analytical ultracentrifugation experiments clearly demonstrate that IgG₁-Fc and sCD16 interact weakly to form a 1:1 complex with an association constant of 1.7 x 10⁵ M^-1 in PBS at 22.0 °C. The thermodynamic parameters, obtained from the temperature dependence of the equilibrium binding constants, exhibit an enthalpy-entropy compensation with a favorable enthalpy at physiological temperatures. The value of -360 cal mol^-1 K^-1 for ∆C_P^° possibly identifies the process as one in which local folding/rearrangement is coupled to complex formation. The 1:1 stoichiometry and thermodynamic parameters provide a basis for understanding the nature of the FcγR-IgG interactions.