title: Variable region domain exchange in human IgGs promotes antibody complex formation with accompanying structural changes and altered effector functions.
abstract: Variable region domain exchanged IgG, or "inside-out (io)," molecules, were produced to investigate the effects of domain interactions on antibody structure and function. Studies using ultracentrifugation and electron microscopy showed that variable region domain exchange induces non-covalent multimerization through Fab domains. Surprisingly, variable region exchange also affected Fc-associated functions such as serum half-life and binding to protein G and FcgammaRI. These alterations were not merely a consequence of IgG aggregation. Both the extent of multimerization and alterations in Fc-associated properties depended on the IgG isotype.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA. lchan@mednet.ucla.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Chan
authors.forename: Martin L
authors.initials: ML
authors.lastname: Phillips
authors.forename: Letitia A
authors.initials: LA
authors.lastname: Wims
authors.forename: K Ryan
authors.initials: KR
authors.lastname: Trinh
authors.forename: Jerrod
authors.initials: J
authors.lastname: Denham
authors.forename: Sherie L
authors.initials: SL
authors.lastname: Morrison
mesh_terms: D000936:Antigen-Antibody Complex; D019281:Dimerization; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000378:metabolism; D011993:Recombinant Fusion Proteins
chemical_list: D000936:Antigen-Antibody Complex; C029152:G-substrate; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D009419:Nerve Tissue Proteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins