Interaction sites on human IgG-Fc for FcgammaR: current models.
Recombinant monoclonal antibodies have entered the clinic as effective in vivo therapeutic. A majority of the therapeutics antibodies employed are intact IgG molecules. IgG-antibody/antigen complexes can activate a wide range of biological responses that result in elimination and destruction of immune complexes. Principle ligands for the activation of clearance (inflammatory) mechanisms are the three types of cellular Fc receptors (FcgammaR) expressed on leucocytes. The effector functions activated by FcgammaR in vivo can be 'orchestrated', in part, through choice of the IgG subclass employed, however, there is potential to customize antibody therapeutics for optimal biological efficacy, in a particular clinical setting, i.e. with respect to the specific disease and the patient response. In order to engineer IgG antibodies and customize their abilities to activate FcgammaR it is necessary to elucidate the molecular specificity of their mutual interactions. This mini-review summarizes our current understanding of interactions of FcgammaRI, FcgammaRII and FcgammaRIII with human IgG antibodies. Particular emphasis is given to the influence of IgG-Fc glycosylation.
Jefferis
Roy
R
Division of Immunity and Infection, The Medical School, University of Birmingham, Edgbaston, Birmingham, UK. r.jefferis@bham.ac.uk
Lund
John
J
D001665:Binding Sites; D002240:Carbohydrate Sequence; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry; D017452:Receptors, IgG / Q000737:chemistry* / Q000378:metabolism*
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D046911:Macromolecular Substances; D020033:Protein Isoforms; D017452:Receptors, IgG