Molecular aspects of human FcgammaR interactions with IgG: functional and therapeutic consequences.
The binding of IgG antibodies to receptors for the Fc region of IgG (FcgammaR) is a critical step for the initiation and/or the control of effector immune functions once immune complexes have been formed. Site-directed and random mutagenesis as well as domain-swapping, NMR and X-ray cristallography have made it possible to get detailed insights in the molecular mechanisms that govern IgG/FcgammaR interactions and to define some of the structural determinants that impact IgG binding to the various FcgammaR. It has demonstrated the role of particular stretches and individual residues located in the lower hinge region of the CH2 domain and in the CH2 and CH3 domains of the Fc region. The importance of the sugar components linked to asparagine 297 in the binding properties of IgG1, the human IgG isotype the most widely used in antibody-based therapies, 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.
Sibéril
Sophie
S
Unité INSERM 255, IFR58, Université René Descartes-Paris 5, Université Pierre et Marie Curie-Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Dutertre
Charles-Antoine
CA
Boix
Charlotte
C
Bonnin
Emmanuelle
E
Ménez
Renée
R
Stura
Enrico
E
Jorieux
Sylvie
S
Fridman
Wolf-Herman
WH
Teillaud
Jean-Luc
JL
D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D016297:Mutagenesis, Site-Directed / Q000379:methods; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc