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Published July 20, 1999 | public
Journal Article

Stoichiometry of the Interaction between the Major Histocompatibility Complex-Related Fc Receptor and Its Fc Ligand

Abstract

The neonatal Fc receptor (FcRn) transports immunoglobulin G (IgG) across epithelia, providing passive immunity and protecting serum IgG from degradation. For both functions, FcRn binds to IgG at the acidic pH of intracellular vesicles (pH ≤ 6.5) and releases IgG at the basic pH of the bloodstream (pH ∼ 7.4). Crystallographic studies show that rat FcRn can interact with the Fc portion of IgG in a repeating array in which FcRn dimers are bridged by Fc fragments to create an "oligomeric ribbon" with a 2n:n stoichiometry. The stoichiometry of the interaction between soluble FcRn and Fc has been reported as either 2:1 for rat FcRn [Huber et al. (1993) J. Mol. Biol. 230, 1077−1083] or 1:1 for mouse FcRn [Popov et al. (1996) Mol. Immunol. 33, 521−530]. To ascertain the reasons for this difference, we analyzed complexes formed in solution between soluble rat or mouse FcRn and Fc. Using a gel-filtration assay under nonequilibrium conditions, we find that both forms of FcRn produce 2:1 receptor−ligand complexes, but that alterations of the carbohydrate moieties on mouse FcRn can result in an apparent stoichiometry of 1:1. However, under equilibrium conditions, all forms of FcRn make complexes with a 2:1 stoichiometry. We conclude that rat and mouse FcRn share the same general ligand binding properties but that small differences in affinities can produce apparent differences under nonequilibrium conditions.

Additional Information

© 1999 American Chemical Society. Received March 30, 1999. Publication Date (Web): June 26, 1999. Supported by a Camille and Henry Dreyfus Teacher Scholar Award (P.J.B.), a grant from the NIH (AI/GM41239 to P.J.B.), and a grant from the Department of Defense Breast Cancer Research Program (L.M.S.). We thank N. E. Simister for the cDNA encoding mFcRn, E. S. Ward, B. Ober, and C. Radu for purified insect cell-derived mFcRn protein, R. A. Marks for NB-DNJ, S. Chamow for the CD4−IgG fusion protein, and members of the Bjorkman lab for critical reading of the manuscript.

Additional details

Created:
August 19, 2023
Modified:
October 25, 2023