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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nechansky, A. Articles by Kricek, F. Search for Related Content PubMed PubMed Citation Articles by Nechansky, A. Articles by Kricek, F.

Inhibition of Antigen-Induced Mediator Release from IgE-Sensitized Cells by a Monoclonal Anti-FcRI -Chain Receptor Antibody: Implications for the Involvement of the Membrane-Proximal -Chain Region in FcRI-Mediated Cell Activation¹

Andreas Nechansky^*, Michael W. Robertson^2,, Bettina A. Albrecht, John R. Apgar and Franz Kricek^2,*

^* Novartis Forschungsinstitut GmbH, Vienna, Austria; and Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037

The interaction between human IgE and its high affinity receptor, FcRI, is a critical event in mediating the allergic response. Aggregation of the -chain of FcRI (FcRI) occurs via cross-linking of receptor-bound IgE by Ag, resulting in cell activation and the release of mediators of hypersensitivity. Recently, we mapped the epitopes of two anti-FcRI mAbs, 15/1 and 5H5F8. In contrast to 15/1, mAb 5H5F8 does not inhibit IgE binding to FcRI. Here we demonstrate both 5H5F8 binding to FcRI⁺ cells as well as a high level of IgE binding to 5H5F8-saturated cells. At the same time 5H5F8 strongly inhibits hexosaminidase release and Ca²⁺ flux after Ag triggering from human IgE-sensitized RBL-2H3 cells stably transfected with human FcRI. Further, 5H5F8 and its Fab inhibit sulfidoleukotriene and histamine release from primary human peripheral blood leukocytes, including cells bearing endogenous IgE. Furthermore, we confirm that 5H5F8 maps to a linear peptide sequence in close proximity to the cell membrane. Two chemically synthesized peptides containing the 5H5F8 epitope sequence PREKY were selected for detailed analysis of 5H5F8 and 5H5F8 Fab binding and were found to produce K_d values of similar magnitude to that observed for binding to recombinant FcRI. These peptides may prove useful as targets for the identification of antagonists of FcRI-mediated biological activity. Moreover, our data indicate that FcRI-mediated activation may involve a novel -chain epitope in an early step of the cell-triggering pathway leading to cellular activation.

This article has been cited by other articles:

				M. VOGEL, E. KELLER-GAUTSCHI, M. J. BAUMANN, P. AMSTUTZ, C. RUF, F. KRICEK, and B. M. STADLER Designed Ankyrin Repeat Proteins as Anti-Idiotypic-Binding Molecules Ann. N.Y. Acad. Sci., August 1, 2007; 1109(1): 9 - 18. [Abstract] [Full Text] [PDF]

				T. Kubota, K. Mukai, Y. Minegishi, and H. Karasuyama Different Stabilities of the Structurally Related Receptors for IgE and IgG on the Cell Surface Are Determined by Length of the Stalk Region in Their {alpha}-Chains. J. Immunol., June 1, 2006; 176(11): 7008 - 7014. [Abstract] [Full Text] [PDF]

				T. Bobrzynski, M. Fux, M. Vogel, M. B. Stadler, B. M. Stadler, and S. M. Miescher A High-Affinity Natural Autoantibody from Human Cord Blood Defines a Physiologically Relevant Epitope on the Fc{epsilon}RI{alpha} J. Immunol., November 15, 2005; 175(10): 6589 - 6596. [Abstract] [Full Text] [PDF]

				J. J. C. Sheu, T. Cheng, H. Y. Chen, C. Lim, and T.-W. Chang Comparative Effects of Human Ig{alpha} and Ig{beta} in Inducing Autoreactive Antibodies Against B Cells in Mice J. Immunol., February 1, 2003; 170(3): 1158 - 1166. [Abstract] [Full Text] [PDF]