Variable region domain exchange in human IgGs promotes antibody complex formation with accompanying structural changes and altered effector functions

• Published in: Molecular immunology Vol. 41; no. 5; pp. 527 - 538
• Main Authors: Chan, Lisa A., Phillips, Martin L., Wims, Letitia A., Trinh, K.Ryan, Denham, Jerrod, Morrison, Sherie L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2004
• Subjects: Antigen-Antibody Complex; Dimerization; Domain exchange; Fab; Function; Humans; IgG; Immunoglobulin; Immunoglobulin Fab Fragments; Immunoglobulin Fc Fragments; Immunoglobulin G - chemistry; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - immunology; Immunoglobulin Variable Region - metabolism; Multimerization; Nerve Tissue Proteins - metabolism; Protein Binding; Protein Structure, Tertiary; Receptors, IgG - metabolism; Recombinant Fusion Proteins; Structure; Variable region; Domain exchange; Function; Variable region; Fab; Multimerization; IgG; Immunoglobulin; Structure
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2004.03.034

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 FcγRI. 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.