Immunoglobulin-fc receptor interactions

Immunoglobulins play a central role in immune protection. They serve as flexible adaptor molecules capable of coupling the recognition of antigenic structures on foreign microorganisms with effector responses that bring about neutralization or elimination of the invading pathogen. There are five classes of immunoglobulin (Ig), namely IgG, IgE, IgA, IgM, and IgD, with differing biological functions and distributions in the body. The function of IgD remains less clear. For IgG, IgA, and IgE, which is the major focus of this chapter, a key element of the Ig effector armory is driven through interaction with specific Fc receptors (FcR) on a variety of immune cells. It considers only the Ce3 and Ce4 domains of IgE and the equivalent domains from IgG and IgA, and shows that there are striking similarities in the overall Fc domain arrangements of the three classes. Each Fc exhibits pseudo two-fold symmetry, and the structure is stabilized principally by non-polar inter-heavy chain interactions between the C-terminal domain pair, and to a lesser extent by interactions between Fc domains in the same heavy chain. The chief differences relate to the positions of the inter-heavy chain disulfide bridges and of the N-linked glycan moieties. Recent years have seen a rapid expansion in the therapeutic use of antibodies. As treatment options broaden and requirements for enhanced Fc functionality intensify, a detailed understanding of Ig-FcR interactions will become ever more important.