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

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 t...

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Bibliographic Details
Published in:Biochemistry (Easton) 1997-08, Vol.36 (31), p.9374-9380
Main Authors: Vaughn, Daniel E., Bjorkman, Pamela J.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Binding Sites
Biosensing Techniques
CHO Cells
Cricetinae
Immunoglobulin G - metabolism
Kinetics
Protein Binding
Rats
Receptors, Fc - metabolism
Recombinant Proteins - metabolism
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Summary: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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi970841r