The Role of the Constant Region in Antibody-Antigen Interactions: Redefining the Modular Model of Immunoglobulin Structure

Immunological canon traditionally divides immunoglobulin molecules into a functionally distinct antigen-binding variable region and a constant region that interacts with downstream components of the immune system. Recent research, along with a reexamination of earlier studies, shows that this modular model of antibody structure is incomplete. Biochemical, structural, and computational studies over the past five decades with many different antibodies illustrate an allosteric antibody model, where conformational changes in the variable region are propagated to the constant region and vice versa. The immunoglobulin constant region is now thought to play a major role in antibody-antigen interactions and can be viewed as another mechanism by which the immune system generates antibody diversity. While a precise structural mechanism is unclear and likely varies by the particular antibody or antibody family, the allosteric antibody model has many implications for the immune response, autoimmunity, vaccine development, and antibody engineering.