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

Raghavan, Malini and Chen, Marcus Y. and Gastinel, Louis N. and Bjorkman, Pamela J. (1994) Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand. Immunity, 1 (4). pp. 303-315. ISSN 1074-7613.

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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.

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Bjorkman, Pamela J.0000-0002-2277-3990
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.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Cancer Research InstituteUNSPECIFIED
Centre National de la Recherche Scientifique (CNRS)UNSPECIFIED
Pew Charitable TrustUNSPECIFIED
Issue or Number:4
Record Number:CaltechAUTHORS:20170405-160734810
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Official Citation:Malini Raghavan, Marcus Y. Chen, Louis N. Gastinel, Pamela J. Bjorkman, Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand, Immunity, Volume 1, Issue 4, 1994, Pages 303-315, ISSN 1074-7613, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75758
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 18:28
Last Modified:03 Oct 2019 16:53

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