IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions.

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Lee CH, Romain G, Yan W, Watanabe M, Charab W, Todorova B, Lee J, Triplett K, Donkor M, Lungu OI, Lux A, Marshall N, Lindorfer MA, Goff ORL, Balbino B, Kang TH, Tanno H, Delidakis G, Alford C, Taylor RP, Nimmerjahn F, Varadarajan N, Bruhns P, Zhang YJ, Georgiou G
Zeitschrift: Nature immunology
Jahr der Veröffentlichung: 2017
ISSN: 1529-2916


Abstract


Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.



FAU-Autoren / FAU-Herausgeber

Lux, Anja Dr.
Lehrstuhl für Genetik
Nimmerjahn, Falk Prof. Dr.
Lehrstuhl für Genetik


Autor(en) der externen Einrichtung(en)
Institut Pasteur
University of Houston
University of Texas at Austin
University of Virginia (UVA)


Zitierweisen

APA:
Lee, C.-H., Romain, G., Yan, W., Watanabe, M., Charab, W., Todorova, B.,... Georgiou, G. (2017). IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions. Nature immunology. https://dx.doi.org/10.1038/ni.3770

MLA:
Lee, Chang-Han, et al. "IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions." Nature immunology (2017).

BibTeX: 

Zuletzt aktualisiert 2018-06-08 um 23:25