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High-Affinity Binding of the Neonatal Fc Receptor to Its IgG Ligand Requires Receptor Immobilization

Vaughn, Daniel E. and Bjorkman, Pamela J. (1997) High-Affinity Binding of the Neonatal Fc Receptor to Its IgG Ligand Requires Receptor Immobilization. Biochemistry, 36 (31). pp. 9374-9380. ISSN 0006-2960. doi:10.1021/bi970841r.

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The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. In adult mammals, FcRn also binds IgG and returns it to the bloodstream, thus protecting IgG from a default degradative pathway. Biosensor assays have been used to characterize the interaction of a soluble form of FcRn with IgG. We use the statistical method of cross-validation to show that there are two classes of noninteracting binding sites, and these are sufficient to account for previously observed nonlinear Scatchard plots of FcRn/IgG binding data. We demonstrate that immobilization of FcRn on the biosensor surface reproduces the high-affinity IgG binding observed for membrane-bound FcRn, whereas immobilization of IgG results in lower affinity binding similar to that of the FcRn/IgG interaction in solution. The dependence of FcRn/IgG binding affinity on the coupled molecule provides further evidence in support of the previously hypothesized model that an FcRn dimer forms the high-affinity IgG binding site.

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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1997 American Chemical Society. Received April 10, 1997; Revised Manuscript Received May 20, 1997. Publication Date (Web): August 5, 1997. Supported by a Camille and Henry Dreyfuss Teacher Scholar Award (P.J.B.) and a grant from the NIH (AI/GM41239 to P.J.B.). We thank Luis Sánchez for providing purified monoclonal antibodies, Malini Raghavan and Robert Karlsson for helpful discussions, and members of the laboratory for critical reading of the manuscript.
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Camille and Henry Dreyfus FoundationUNSPECIFIED
Issue or Number:31
Record Number:CaltechAUTHORS:20170406-103839667
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Official Citation:High-Affinity Binding of the Neonatal Fc Receptor to Its IgG Ligand Requires Receptor Immobilization Daniel E. Vaughn and Pamela J. Bjorkman Biochemistry 1997 36 (31), 9374-9380 DOI: 10.1021/bi970841r
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75801
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 17:56
Last Modified:15 Nov 2021 16:36

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