HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ding, J. W. Articles by Chong, A. S. Search for Related Content PubMed PubMed Citation Articles by Ding, J. W. Articles by Chong, A. S.

Hyperacute Rejection by Anti-Gal IgG₁, IgG_2a, and IgG_2b Is Dependent on Complement and Fc- Receptors¹

Jin Wen Ding^*, Tingting Zhou^*, Huasong Zeng^*, Lianli Ma^*, J. Sjef Verbeek, Dengping Yin^*, Jikun Shen^* and Anita S. Chong^2,*

^* Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL 60637; and Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

We have previously reported that anti-Gal-1,3Gal (Gal) IgG3 mAbs mediate a classical complement-dependent hyperacute rejection (HAR), while anti-Gal IgG1 mAbs mediate HAR that is dependent on complement, the Fc- receptors FcRII/III (CD32/CD16), and NK cells. IgG2a and IgG2b subclasses can activate complement and have FcR binding properties in vitro. Whether these IgG subclasses can mediate HAR in vivo and the mechanisms by which they would do so are not known. In this study, we isolated spontaneous IgG switch mutants from an anti-Gal IgG1 hybridoma. In vitro complement-mediated hemolytic assays with mouse complement indicate that both anti-Gal IgG2a and IgG2b mAbs were more potent compared with the parent anti-Gal IgG1. In vivo administration of anti-Gal IgG2a and IgG2b mAbs into Gal^–/– mice induced HAR of rat cardiac xenografts. HAR induced by anti-Gal IgG2a and IgG2b was dependent on complement activation and the presence of NK cells. Using FcRIII-deficient (Gal^–/–CD16^–/–) recipients, we observed that HAR mediated by different anti-Gal IgG subclasses was variably dependent on FcRIII, with IgG1 > IgG2b >> IgG2a = IgG3. Using FcRI-deficient (Gal^–/–CD64^–/–) recipients, we observed that HAR mediated by anti-Gal IgG1, IgG2a, and IgG2b, but not by anti-Gal IgG3, was dependent on FcRI. Collectively, these studies demonstrate the necessity and sufficiency of complement in IgG3-mediated HAR and the necessity of both complement and FcR, especially FcRI, in IgG1-, IgG2a-, and IgG2b-mediated HAR.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the National Institutes of Health (R01 AI52464) to A.S.C.

² Address correspondence and reprint requests to Dr. Anita S. Chong, Department of Surgery, Section of Transplantation, MC5026, University of Chicago, Chicago, IL 60637. E-mail address: achong{at}uchicago.edu

³ Abbreviations used in this paper: HAR, hyperacute rejection; CVF, cobra venom factor; Gal, Gal-1,3Gal; vWF, von Willebrand’s factor.

This article has been cited by other articles:

				T. Iuchi, S. Teitz-Tennenbaum, J. Huang, B. G. Redman, S. D. Hughes, M. Li, G. Jiang, A. E. Chang, and Q. Li Interleukin-21 Augments the Efficacy of T-Cell Therapy by Eliciting Concurrent Cellular and Humoral Responses Cancer Res., June 1, 2008; 68(11): 4431 - 4441. [Abstract] [Full Text] [PDF]