Flexibility of human IgG subclasses.
A variable region (Id)-matched set of genetically engineered human IgG1, -2, -3, and -4 subclass molecules was analyzed by electron microscopy for hinge-mediated differences in flexibility. The hinge-mediated bending was studied, as was the ability of the subclasses to form immune complexes with two anti-Id mAbs. The data show that the rank order (most to least flexible) of the IgG subclasses for hinge-folding mode of flexibility between Fab arms is IgG3 > IgG1 > IgG4 > IgG2. The mean Fab-Fab angles for the subclasses are IgG3, 136 degrees; IgG4, 128 degrees; IgG2, 127 degrees; and IgG1, 117 degrees. Fab-Fc angles were similarly analyzed. By sampling of equimolar mixtures of Id-bearing IgGs and each of two anti-Id mAb after incubation over time (1.5 min to 3.5 h), different kinetic profiles of immune complex formation of defined geometry were documented. Both anti-Id mAbs displayed unique kinetic profiles when complexed with the four IgG subclass molecules but also shared important features. Most notable was the higher propensity to form closed bivalent ring Id-anti-Id dimers with IgG3 than with IgG2 and IgG4. IgG1 was intermediate in its ability to form such dimers.
Roux
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KH
Department of Biological Science, Structural Biology Program, Florida State University, Tallahassee 32306, USA. roux@bio.fsu.edu
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Michaelsen
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D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000936:Antigen-Antibody Complex / Q000737:chemistry; D002460:Cell Line; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007130:Immunoglobulin Idiotypes / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D051379:Mice; D017510:Protein Folding; D013329:Structure-Activity Relationship
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; C048844:anti-IgG