title: Human constant regions influence the antibody binding characteristics of mouse-human chimeric IgG subclasses.
abstract: Although antibody affinity is primarily determined by immunoglobulin variable region structure human IgG antibodies of the four subclasses specific for the same antigen have been shown to differ in their affinity. To explore the influence of the immunoglobulin constant region on functional antibody affinity, a set of V region identical mouse-human chimeric IgG subclasses specific for TAG72 (tumour-associated glycoprotein) were studied. Biomolecular interaction analysis (BIA) was used to determine the binding kinetics of whole IgG subclasses and F(ab')2 fragments. Despite identical V regions, binding kinetics differed for the four subclasses. The apparent dissociation rate constants of the intact immunoglobulins ranked IgG4 < IgG3 < IgG2 < IgG1. In contrast, analysis of the binding characteriztics of the F(ab')2 fragments derived from IgG1, IgG2 and IgG4 revealed identical binding kinetics. The structure of the constant regions of the humanized IgG subclass antibodies clearly influenced functional antibody affinity, as has been described for the murine IgG subclasses. The exact mechanism for this phenomenon remains obscure but such differences should be taken into account when designing or choosing antibodies for therapeutic use.
authors.affiliation: Institute of Child Health, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: McCloskey
authors.forename: M W
authors.initials: MW
authors.lastname: Turner
authors.forename: P
authors.initials: P
authors.lastname: Steffner
authors.forename: R
authors.initials: R
authors.lastname: Owens
authors.forename: D
authors.initials: D
authors.lastname: Goldblatt
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D002460:Cell Line; D002678:Chimera / Q000276:immunology*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D051379:Mice
chemical_list: D007127:Immunoglobulin Constant Regions; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G