title: FcgammaR: The key to optimize therapeutic antibodies?
abstract: The binding of IgG to receptors for the Fc region of IgG (FcgammaR) is a critical step for the initiation and the control of effector immune functions. Activating FcgammaR induce antibody-dependent cell cytotoxicity (ADCC), endocytosis of immune complexes followed by antigen presentation, phagocytosis, and release of cytokines or pro-inflammatory mediators. By contrast, inhibitory FcgammaR regulate immune responses by inhibiting the activation of B lymphocytes, monocytes, mast cells and basophils, induced through activating receptors. Studies with FcgammaR-deficient mice support the critical role of the different FcgammaR in the in vivo functional effects of therapeutic monoclonal antibodies. Structural studies have provided detailed insights in the molecular mechanisms that govern IgG/FcgammaR interactions. The importance of the sugar components linked to asparagine 297 in the function of IgG has been also highlighted. These data have led to the engineering of a new generation of monoclonal antibodies for therapeutic use with optimized effector functions.
authors.affiliation: Unité INSERM 255, IFR58, Université René Descartes-Paris 5, Université Pierre et Marie Curie-Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sibéril
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Dutertre
authors.forename: Wolf-Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Teillaud
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D006801:Humans; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017452:Receptors, IgG