Do Water Molecules Displaced by Hydrophobic Interactions Stabilize Antigen-Antibody Binding?

Abstract

Background: Antigen-antibody reactions are a special field of molecular interactions. The physicochemical nature of antigen-antibody binding and ligand-induced changes in the fine molecular structures of antigens during immunocomplex formation are less studied. However, these changes in the molecular appearance are extremely important for further molecular recognition. The major aim of this study is to clarify the physico-chemical modification of the antigen/hapten during immunobinding using model experiments. Methods: An appropriate model system was designed for our investigations: fluorescein-isothiocyanate (FITC, isomer I) was used as the antigen (hapten), and its interactions with a specific antibody (monoclonal anti-FITC IgG1) were analyzed using spectrophotometry, different spectrofluorimetric methods and fluorescence polarization, and Fourier-transform infrared spectroscopic methods. Results: Fluorescent polarization and infrared spectroscopic measurements detected a local decrease in the hydration degree in the submolecular area of the specific ligand between the small antigen (hapten) molecule and the hypervariable region of the specific IgG1, causing “rigidization” of molecular movements. Changes in hydration modified the molecular microenvironment, allowing them to influence further functions of both immunoglobulins and the antigen. Conclusion: Hydrophobic interactions with exclusion of water molecules around the binding sites seem to be thermodynamically strong enough for stable molecular binding without a covalent chemical interaction between the antigen and the antibody. The results of this study, together with data obtained in previous research, help understand the molecular dynamics of the antigen-antibody reaction better.