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Published July 1994 | metadata_only
Journal Article

Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand


The neonatal Fc receptor (FcRn) is structurally similar to class 1 major histocompatibility molecules. FcRn transports maternal immunoglobulin G (IgG) from ingested milk into the blood. IgG is bound at the pH of milk (pH 6.0–6.5) in the gut and released at the pH of blood (pH 7.5). We find that alteration of a histidine pair within the α3 domain of FcRn and of a nearby loop (the FcRn counterpart of the class I CD8-binding loop) affects the affinity for IgG. Inhibition studies suggest the involvement of the FcRn B_2-microglobulin domain in IgG binding. Fragment B of protein A inhibits FcRn binding to IgG, localizing the binding site on Fc for FcRn to the C_H2-C_H3 domain interface. Three histidines present at the C_H2-C_H3 domain interface of Fc could be partially responsible for the pH-dependent interaction between FcRn and IgG.

Additional Information

© 1994 Cell Press. Received 25 April 1994, Revised 19 May 1994. We thank W. Burmeister for helpful discussions about the FcRn structure; W. Burmeister and K. Zinn for critical reading of the manuscript; S. Ou and the Caltech MAb facility; R. Diamond and the Caltech cell sorting facility; C. Esau for purification of FcRn and help with the construction of the H250Q-H251N mutant; B. Kelley and P. Carter for purified fragment B of protein A and pFc' fragment; J. A. Kake and O. H. Griffith for the bacteria producing phosphatidylinositol-specific phospholipase C; and S. Davis of Pharmacia Biosensor for help with the BIAcore data. Supported by the Howard Hughes Medical Institute (L. N. G., P. J. B.), a postdoctoral fellowship from the Cancer Research Institute (M. R.), and the Centre National de la Recherche Scientifique (L. N. G.). P. J. B. was a Pew Scholar and had a Young Investigator Award from the Cancer Research Institute during part of the work.

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August 20, 2023
August 20, 2023