Synthetic haptens as probes of antibody response and immunorecognition

The molecular forces that bind antibody to antigen have long fascinated chemists. The use of synthetic haptens to study immunochemical phenomena can be traced back to the classic work of Karl Lansteiner. His utilization of small-molecule-protein conjugates first demonstrated the shape-selective nature of antibody binding. Later work by Linus Pauling and David Pressman employed multivalent, synthetic ligands to establish the bivalent nature of Antibodies and explain the nature of immunoprecipitation. Fluorescent probes such as dansyl, fluorescein, and Ru(bpy)(2+)(3) have been used to study affinity maturation, quantify antibody affinities, and investigate polyclonal antibody heterogeneity. Finally, X-ray crystallography has yielded a molecular picture of how Antibodies exercise intermolecular forces (e.g., charge-charge interactions, H-bonding, and Van der Waals) to bind haptens. Studies inspired by Landsteiner's original work continue to play an important role in fields ranging from immunodiagnostics to catalytic Antibodies.