The influence of the hinge region length in binding of human IgG to human Fcgamma receptors.
Interactions between human IgG with human FcgammaRI and FcgammaRIIa (R131) were studied to investigate the role of the hinge region of IgG3 and IgG1 in the binding of the antibodies to FcgammaR. It was found that a hinge deletion mutant of IgG3 (IgG3 m15) was reduced in its ability to bind to FcgammaRI and FcgammaRIIa but was more potent at activating ADCC by activated lymphocytes (FcgammaRIIIa-mediated), compared to the wild-type version of IgG3. The human IgG1 allotype G1m(a,z) was more efficient at binding to FcgammaRI than the two IgG3 antibodies tested. The IgG1 and IgG3 wild type antibodies were better able to bind to FcgammaRII than the hinge deletion mutant version of IgG3. The data suggest a role for the hinge region in influencing FcgammaR mediated effector functions in IgG3.
Redpath
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S
Department of Pathology, University of Cambridge, UK.
Michaelsen
T E
TE
Sandlie
I
I
Clark
M R
MR
D000595:Amino Acid Sequence; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm; D001667:Binding, Competitive; D000074301:CD52 Antigen; D002460:Cell Line; D019281:Dimerization; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; C000613864:Cd52 protein, rat; C080568:Fc gamma receptor IIA; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D017452:Receptors, IgG