2001 年 121 巻 5 号 p. 345-354
Fcγ Receptors (FcγR) are membrane glycoproteins that bind the Fc portion of immunoglobulin G (IgG). The cross linking of FcγR-bound IgG by multivalent antigens allows clustering of the FcγR and initiates a variety of effector mechanisms which play a key role in immune defenses against pathogens. The Fc region is composed of two identical polypeptide chains, which are related to each other by a two-fold axis. Recent elucidation of the crystal structure of human FcγRII provided two distinct views of modes of IgG-FcγR interactions, which is controversial against each other. Nuclear magnetic resonance (NMR) spectroscopy provides a unique and irreplaceable tool to solve these issues. We recently studied the interaction between the Fc fragment of mouse IgG2b and the extracellular domain of mouse FcγRII by this method. We showed that FcγRII binds to a negatively charged area of the CH2 domain, corresponding to the lower hinge region, and that the binding of FcγRII onto one of the two symmetrically related sites on the Fc induces a conformational change in the other site. This conformational change may account for the 1:1 stoichiometry that we and others observed between FcγR and Fc. We therefore propose a model that explains why the interaction between IgG molecules and FcγR does not trigger cellular responses in the absence of cross linking by multivalent antigens and does not lead to spontaneous inflammatory responses that would be deleterious for the organism.