| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 158, Issue 5 2211-2217, Copyright © 1997 by American Association of Immunologists
ARTICLES |
C Medesan, D Matesoi, C Radu, V Ghetie and ES Ward
Department of Microbiology and Cancer Immunobiology Center, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
The MHC class I-related receptor, FcRn, is involved in both the transcytosis of serum gamma-globulins (IgGs) and in regulating their serum persistence. The interaction site of FcRn on the Fc region of rodent IgG has been mapped to residues at the CH2-CH3 domain interface using site-directed mutagenesis and x-ray crystallographic analyses. In the current study, the role of individual residues (H310, H433, and N434) at this interface in mediating the Fc-FcRn interaction has been investigated using recombinant, mutated Fc hinge fragments derived from mouse IgG1. In addition, two highly conserved Fc histidines (H435 and H436) have been mutated to alanine, and the resulting mutated Fc hinge fragments were analyzed in both transcytosis and pharmacokinetic studies in mice and in competition binding assays using recombinant, soluble FcRn. The analyses indicate that mutation of H310, H435, and, to a lesser extent, H436 to alanine results in reduced activity of the Fc hinge fragments in both in vivo and in vitro assays. Thus, in addition to the previously defined role of 1253 in the FcRn-IgG interaction, these histidines play a key role in mediating the functions conducted by this Fc receptor. The effects of these mutations on binding of Fc hinge fragments to staphylococcal protein A have also been analyzed and demonstrate a partial, but not complete, overlap of the FcRn and staphylococcal protein A interaction sites on mouse IgG1.
This article has been cited by other articles:
|
|
 |
|
  W. Mi, S. Wanjie, S.-T. Lo, Z. Gan, B. Pickl-Herk, R. J. Ober, and E. S. Ward Targeting the Neonatal Fc Receptor for Antigen Delivery Using Engineered Fc Fragments J. Immunol., December 1, 2008; 181(11): 7550 - 7561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Qiao, K. Kobayashi, F.-E. Johansen, L. M. Sollid, J. T. Andersen, E. Milford, D. C. Roopenian, W. I. Lencer, and R. S. Blumberg Dependence of antibody-mediated presentation of antigen on FcRn PNAS, July 8, 2008; 105(27): 9337 - 9342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Natsume, M. In, H. Takamura, T. Nakagawa, Y. Shimizu, K. Kitajima, M. Wakitani, S. Ohta, M. Satoh, K. Shitara, et al. Engineered Antibodies of IgG1/IgG3 Mixed Isotype with Enhanced Cytotoxic Activities Cancer Res., May 15, 2008; 68(10): 3863 - 3872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Knogler, J. Grunberg, K. Zimmermann, S. Cohrs, M. Honer, S. Ametamey, P. Altevogt, M. Fogel, P. A. Schubiger, and I. Novak-Hofer Copper-67 Radioimmunotherapy and Growth Inhibition by Anti-L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis Clin. Cancer Res., January 15, 2007; 13(2): 603 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vaccaro, R. Bawdon, S. Wanjie, R. J. Ober, and E. S. Ward Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies PNAS, December 5, 2006; 103(49): 18709 - 18714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Petkova, S. Akilesh, T. J. Sproule, G. J. Christianson, H. Al Khabbaz, A. C. Brown, L. G. Presta, Y. G. Meng, and D. C. Roopenian Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease Int. Immunol., December 1, 2006; 18(12): 1759 - 1769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Hinton, J. M. Xiong, M. G. Johlfs, M. T. Tang, S. Keller, and N. Tsurushita An Engineered Human IgG1 Antibody with Longer Serum Half-Life J. Immunol., January 1, 2006; 176(1): 346 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Ward, C. Martinez, C. Vaccaro, J. Zhou, Q. Tang, and R. J. Ober From Sorting Endosomes to Exocytosis: Association of Rab4 and Rab11 GTPases with the Fc Receptor, FcRn, during Recycling Mol. Biol. Cell, April 1, 2005; 16(4): 2028 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Kenanova, T. Olafsen, D. M. Crow, G. Sundaresan, M. Subbarayan, N. H. Carter, D. N. Ikle, P. J. Yazaki, A. F. Chatziioannou, S. S. Gambhir, et al. Tailoring the Pharmacokinetics and Positron Emission Tomography Imaging Properties of Anti-Carcinoembryonic Antigen Single-Chain Fv-Fc Antibody Fragments Cancer Res., January 15, 2005; 65(2): 622 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ober, C. Martinez, X. Lai, J. Zhou, and E. S. Ward Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level PNAS, July 27, 2004; 101(30): 11076 - 11081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Hinton, M. G. Johlfs, J. M. Xiong, K. Hanestad, K. C. Ong, C. Bullock, S. Keller, M. T. Tang, J. Y. Tso, M. Vasquez, et al. Engineered Human IgG Antibodies with Longer Serum Half-lives in Primates J. Biol. Chem., February 20, 2004; 279(8): 6213 - 6216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ober, C. Martinez, C. Vaccaro, J. Zhou, and E. S. Ward Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn J. Immunol., February 15, 2004; 172(4): 2021 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Ward, J. Zhou, V. Ghetie, and R. J. Ober Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans Int. Immunol., February 1, 2003; 15(2): 187 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Spiekermann, P. W. Finn, E. S. Ward, J. Dumont, B. L. Dickinson, R. S. Blumberg, and W. I. Lencer Receptor-mediated Immunoglobulin G Transport Across Mucosal Barriers in Adult Life: Functional Expression of FcRn in the Mammalian Lung J. Exp. Med., August 5, 2002; 196(3): 303 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ober, C. G. Radu, V. Ghetie, and E. S. Ward Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies Int. Immunol., December 1, 2001; 13(12): 1551 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Firan, R. Bawdon, C. Radu, R. J. Ober, D. Eaken, F. Antohe, V. Ghetie, and E. S. Ward The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of {gamma}-globulin in humans Int. Immunol., August 1, 2001; 13(8): 993 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wright, Y. Sato, T. Okada, K. H. Chang, T. Endo, and S. L. Morrison In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure Glycobiology, December 1, 2000; 10(12): 1347 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. DeLano, M. H. Ultsch, A. M. de Vos, and J. A. Wells Convergent Solutions to Binding at a Protein-Protein Interface Science, February 18, 2000; 287(5456): 1279 - 1283. [Abstract] [Full Text]
|
|
|
|
|
|
S. D. Gillies, Y. Lan, K.-M. Lo, M. Super, and J. Wesolowski Improving the Efficacy of Antibody-Interleukin 2 Fusion Proteins by Reducing Their Interaction with Fc Receptors Cancer Res., May 1, 1999; 59(9): 2159 - 2166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Praetor, I Ellinger, and W Hunziker Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells J. Cell Sci., January 7, 1999; 112(14): 2291 - 2299. [Abstract] [PDF]
|
|
|
|
|
|
R. L. Shields, A. K. Namenuk, K. Hong, Y. G. Meng, J. Rae, J. Briggs, D. Xie, J. Lai, A. Stadlen, B. Li, et al. High Resolution Mapping of the Binding Site on Human IgG1 for Fcgamma RI, Fcgamma RII, Fcgamma RIII, and FcRn and Design of IgG1 Variants with Improved Binding to the Fcgamma R J. Biol. Chem., February 23, 2001; 276(9): 6591 - 6604. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
