Stoichiometry and thermodynamics of the interaction between the Fc fragment of human IgG1 and its low-affinity receptor Fc gamma RIII.

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 huFc gamma RIII (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 10(5) M-1 in PBS at 22.0 degrees 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 delta Cp zero 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 Fc gamma R-IgG interactions.