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Ligand Valency Affects Transcytosis, Recycling and Intracellular Trafficking Mediated by the Neonatal Fc Receptor

Tesar, Devin B. and Tiangco, Noreen E. and Bjorkman, Pamela J. (2006) Ligand Valency Affects Transcytosis, Recycling and Intracellular Trafficking Mediated by the Neonatal Fc Receptor. Traffic, 7 (9). pp. 1127-1142. ISSN 1398-9219. PMCID PMC1618808. doi:10.1111/j.1600-0854.2006.00457.x.

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The neonatal Fc receptor (FcRn) transports IgG across epithelial cell barriers to provide maternal antibodies to offspring and serves as a protection receptor by rescuing endocytosed IgG and albumin from lysosomal degradation. Here we describe the generation of polarized Madin–Darby canine kidney (MDCK) cells expressing rat FcRn (rFcRn) to investigate the potential requirement for ligand bivalency in FcRn-mediated transport. The rFcRn-MDCK cells bind, internalize and bidirectionally transcytose the bivalent ligands IgG and Fc across polarized cell monolayers. However, they cannot be used to study FcRn-mediated transport of the monovalent ligand albumin, as we observe no specific binding, internalization or transcytosis of rat albumin. To address whether ligand bivalency is required for transport, the ability of rFcRn to transcytose and recycle wild-type Fc homodimers (wtFc; two FcRn-binding sites) and a heterodimeric Fc (hdFc; one FcRn-binding site) was compared. We show that ligand bivalency is not required for transcytosis or recycling, but that wtFc is transported more efficiently than hdFc, particularly at lower concentrations. We also demonstrate that hdFc and wtFc have different intracellular fates, with more hdFc than wtFc being trafficked to lysosomes and degraded, suggesting a role for avidity effects in FcRn-mediated IgG transport.

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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2006 The Authors. Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. Received 10 December 2005, revised and accepted for publication 25 May 2006. Published article online 29 June 2006; Issue online 29 June 2006 We thank W. Lance Martin for construction of expression vectors, Shelley Diamond of the Caltech Cell Sorting Facility for assistance in the analysis of cell lines, Enrique Rodriguez-Boulan and Lennart Lögdberg for the AC17 and 2B10C11 antibodies, Keith Mostov for the MDCK II cells, and Elaine Bearer and members of the Bjorkman lab for critical reading of the manuscript. This work was supported by the National Institutes of Health (2 R37 AI041239-06A1 to P.J.B.).
Subject Keywords:apical, basolateral, FcRn, FcRn-GFP, heterodimeric Fc (hdFc), IgG, Madin–Darby canine kidney (MDCK) cells, transcytosis
Issue or Number:9
PubMed Central ID:PMC1618808
Record Number:CaltechAUTHORS:TEStraf06
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6261
Deposited By: Archive Administrator
Deposited On:29 Nov 2006
Last Modified:08 Nov 2021 20:32

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