Entropy-favored human antibody binding reactions with a non-infectious antigen

Little is known about the thermodynamic properties of human antibodies directed against ‘natural’ antigen surfaces, possibly due to the complex interactions that are involved. Using an affinity distribution method, we have previously characterized the binding reactions between a major allergen from ragweed, Amb a 1, and serum Amb a 1-specific IgE as a model system. We determined the temperature dependence of these interactions using serum samples from people with established allergic sensitivity to ragweed pollen. Each sample provided evidence for three epitope-specific IgE reactions with extremely high equilibrium binding affinities @ 37 °C (108 to 1011 M−1). Determining the affinities over a range of temperatures (4–41 °C) revealed a favorable exothermic Gibbs free energy change, ΔG ≈ −17.59 (± 5.04) kcal/M, comparable to previous reports using monoclonal antibodies produced against well-defined artificial antigens. In contrast to previous studies, in this system there was minimal input from enthalpy: ΔH ≈ −2.41 (± 2.32) kcal/M. However, a significant contribution was found from entropic changes: ΔS ≈ 48.98 (± 9.20) cal/K M. Human ‘secondary antibodies’ such as IgE, produced after exposure to ‘natural’ antigens, are optimized in terms of their high equilibrium binding constants with the antigen (allergen) that induced their production. Thermodynamically this is exemplified by minimal enthalpic (bond formation) concomitant with significant entropic (alignment) contributions to the total free energy change of reaction. These results suggest a high degree of ‘complementarity’ between the antibody and antigen surfaces in this experimental system, and may be a general guiding principle in the evolution of antibody repertoires by the adaptive immune system.