• Immunotherapy medications often utilize fragments of a monoclonal immunoglobulin rather than the full immunoglobulin; because fragments are smaller, they typically have better tissue penetration and pharmacokinetics. Fab fragments contain a variable domain and the first constant region from a heavy and light chain; because they do not contain an Fc receptor, Fab fragments cannot trigger cell killing via complement or phagocytosis.
• IgG, IgA, and IgD also have a hinge region between the Fab and the Fc fragments. The hinge region is rich in cysteine and proline amino acids, which provide significant flexibility to the immunoglobulin and allow greater movement of the Fab fragment arms. Fab fragments with long hinge regions are better able to reach multiple epitopes on an antigen; this increases immunoglobulin avidity because avidity is directly proportional to the number of Fab-antigen interactions. However, long hinge regions are more susceptible to destruction by bacterial proteases (eg, IgA protease).