Structural Heterogeneity and Functional Domains of Murine Immunoglobulin G Fc Receptors

TLDR

Binding of antibodies to effector cells via Fc receptors is central to antigen clearance, and the encoded proteins belong to the immunoglobulin supergene family, most homologous to MHC molecule Eβ. The study characterizes the structure and function of murine IgG Fc receptors by molecular analysis of FcR specific for the IgG isotype. Two genes encode Fc receptors that, via alternative splicing, generate molecules with conserved extracellular domains but distinct transmembrane and cytoplasmic regions, and transfection of individual FcR genes shows that ligand‑binding requirements are encoded within a single gene. The studies reveal that the molecular basis of FcR functional heterogeneity allows different signals to be transduced in response to a single ligand.

Abstract

Binding of antibodies to effector cells by way of receptors to their constant regions (Fc receptors) is central to the pathway that leads to clearance of antigens by the immune system. The structure and function of this important class of receptors on immune cells is addressed through the molecular characterization of Fc receptors (FcR) specific for the murine immunoglobulin G isotype. Structural diversity is encoded by two genes that by alternative splicing result in expression of molecules with highly conserved extracellular domains and different transmembrane and intracytoplasmic domains. The proteins encoded by these genes are members of the immunoglobulin supergene family, most homologous to the major histocompatibility complex molecule E β . Functional reconstitution of ligand binding by transfection of individual FcR genes demonstrates that the requirements for ligand binding are encoded in a single gene. These studies demonstrate the molecular basis for the functional heterogeneity of FcR's, accounting for the possible transduction of different signals in response to a single ligand.