Ligand valency affects transcytosis, recycling and intracellular trafficking mediated by the neonatal Fc receptor.
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.
Tesar
Devin B
DB
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Tiangco
Noreen E
NE
Bjorkman
Pamela J
PJ
D000818:Animals; D002460:Cell Line; D004285:Dogs; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D007074:Immunoglobulin G / Q000378:metabolism*; D008024:Ligands; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011961:Receptors, Fc / Q000235:genetics / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D011961:Receptors, Fc; C100688:Fc receptor, neonatal