A non-classical view of antibody properties: Allosteric effect between variable and constant regions.

Historically, antibodies have been divided into two functionally independent domains, the variable (V) region for antigen binding and the constant (C) region for mediating effector functions. However, this classical view of antibody function has been severely challenged by a large and growing number of studies, which reveal long-range conformational interactions and allosteric links between the V and C regions. This review comprehensively summarizes the existing studies on antibody allostery, including allosteric conformational changes induced by covalent modifications or noncovalent ligand binding. In addition, we discuss how intramolecular allosteric signals are transmitted from the V to C regions and vice versa. This review argues that there is sufficient evidence to revisit the structure-function relationship of antibodies. These advances in antibody allostery will provide a blueprint for regulating antibody functions in a simple and highly predictable manner. More focus on antibody allostery will definitely benefit antibody engineering and vaccine design in the field of biotechnology.