The Fc valency of an immune complex is the decisive factor for binding to low‐affinity Feγ receptors

Abstract

Tetanus toxoid (TT) was complexed with two human monoclonal antibodies. The antibodies recognized different, nonrepeating epitopes. The complexes formed were characterized by gel filtration and isokinetic sucrose density gradient centrifugation. It was found that in antigenic excess the separate antibodies formed a complex of one antibody molecule and two TT molecules [IgG1-(TT)2 and IgG3-(TT)2]. In cases where equal amounts of TT and both antibodies were mixed, a dimeric complex [IgG1-(TT)2-IgG3] was formed. The binding of these immune complexes to human neutrophils and eosinophils was studied. Whereas the immune complexes containing one antibody did not bind to either cell type, the two-antibody complex bound to both. This indicates that not the sterical change in the Fc part of an antibody molecule after binding an antigen, but the Fc valency of an immune complex is the decisive factor in Fc receptor interaction with neutrophilic and eosinophilic granulocytes.

Estrogenic effect on swelling and monocytic receptor expression in an arthritic temporomandibular joint model

“…CD16 binding is preferential for small immunoglobulin G (IgG) dimer or trimer complexes that include anti-IgG antibody complexes. This is an important component of auto-antigens and arthritic factors that are potential triggers for onset or maintenance of arthritic diseases [29,[30][31][32]. Importantly, significantly high levels of auto-antigens have been detected in the synovial fluid of TMD patients in comparison to healthy individuals [33] and previous studies have shown that CD16 expression and cytokine release are modulated in monocytes/macrophages by estrogen treatment [34].…”

17β‐estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte‐derived macrophages

“…The functional CD16 receptor consists of two subunits: an ␣ subunit that spans the membrane and functions in binding antigen, and a ␥ subunit (FcRI␥) necessary for receptor assembly and signal transduction (22). Importantly, CD16 binding is preferential for small IgG dimer or trimer complexes that include IgG-anti-IgG antibody complexes, an important component of rheumatoid factors that are potential triggers for onset or maintenance of RA (23)(24)(25)(26). Furthermore, expression of CD16 on macrophages is restricted to tissues (e.g., synovial tissue, pericardium) impacted by RA, suggesting that the tissue specificity of RA occurs through a mechanism dependent on this receptor (27).…”

Induction of tumor necrosis factor α production by adhered human monocytes: A key role for Fcγ receptor type IIIA in rheumatoid arthritis

“…Fc␥RI (CD64), also functionally associated with large complexes, is only expressed at low levels, being inducible by interferon-␥ (15). Furthermore, Fc␥RIII has been shown to preferentially bind small immune complexes (17). Furthermore, Fc␥RIII has been shown to preferentially bind small immune complexes (17).…”