CDB25:0003774 IGHG1 — FCGR3B
Experimentally validated in Human; Orthology-inferred in Frog, Zebrafish, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex.
Nature, 2000; PubMed, Homo sapiens IGHG1 — Homo sapiens FCGR3B
ABSTRACT: The immune response depends on the binding of opsonized antigens to cellular Fc receptors and the subsequent initiation of various cellular effector functions of the immune system. Here we describe the crystal structures of a soluble Fc gamma receptor (sFc gammaRIII, CD16), an Fc fragment from human IgG1 (hFc1) and their complex. In the 1:1 complex the receptor binds to the two halves of the Fc fragment in contact with residues of the C gamma2 domains and the hinge region. Upon complex formation the angle between the two sFc gammaRIII domains increases significantly and the Fc fragment opens asymmetrically. The high degree of amino acid conservation between sFc gammaRIII and other Fc receptors, and similarly between hFc1 and related immunoglobulins, suggest similar structures and modes of association. Thus the described structure is a model for immune complex recognition and helps to explain the vastly differing affinities of other Fc gammaR-IgG complexes and the Fc epsilonRI alpha-IgE complex.
Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses.
Blood, 2009; PubMed, Homo sapiens IGHG1 — Homo sapiens FCGR3B
ABSTRACT: Distinct genes encode 6 human receptors for IgG (hFcgammaRs), 3 of which have 2 or 3 polymorphic variants. The specificity and affinity of individual hFcgammaRs for the 4 human IgG subclasses is unknown. This information is critical for antibody-based immunotherapy which has been increasingly used in the clinics. We investigated the binding of polyclonal and monoclonal IgG1, IgG2, IgG3, and IgG4 to FcgammaRI; FcgammaRIIA, IIB, and IIC; FcgammaRIIIA and IIIB; and all known polymorphic variants. Wild-type and low-fucosylated IgG1 anti-CD20 and anti-RhD mAbs were also examined. We found that (1) IgG1 and IgG3 bind to all hFcgammaRs; (2) IgG2 bind not only to FcgammaRIIA(H131), but also, with a lower affinity, to FcgammaRIIA(R131) and FcgammaRIIIA(V158); (3) IgG4 bind to FcgammaRI, FcgammaRIIA, IIB and IIC and FcgammaRIIIA(V158); and (4) the inhibitory receptor FcgammaRIIB has a lower affinity for IgG1, IgG2, and IgG3 than all other hFcgammaRs. We also identified parameters that determine the specificity and affinity of hFcgammaRs for IgG subclasses. These results document how hFcgammaR specificity and affinity may account for the biological activities of antibodies. They therefore highlight the role of specific hFcgammaRs in the therapeutic and pathogenic effects of antibodies in disease.