Localization of the binding site for the human high-affinity Fc receptor on IgG

Alexander R. Duncan; Jennifer M. Woof; Lynda J. Partridge; Dennis R. Burton; Greg Winter

doi:10.1038/332563a0

Localization of the binding site for the human high-affinity Fc receptor on IgG

Alexander R. Duncan, Jennifer M. Woof, Lynda J. Partridge, Dennis R. Burton, Greg Winter

DArcy Thompson Unit

Research output: Contribution to journal › Article › peer-review

280 Citations (Scopus)

Abstract

A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligo-nucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235 → Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen.

Original language	English
Pages (from-to)	563-564
Number of pages	2
Journal	Nature
Volume	332
Issue number	6164
DOIs	https://doi.org/10.1038/332563a0
Publication status	Published - 7 Apr 1988

Keywords

Amino Acid Sequence
Animals
Binding Sites
Humans
Immunoglobulin G/metabolism
Leukocytes, Mononuclear/metabolism
Mice
Molecular Sequence Data
Protein Conformation
Receptors, Fc/metabolism
Receptors, IgG

ASJC Scopus subject areas

General

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10.1038/332563a0

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title = "Localization of the binding site for the human high-affinity Fc receptor on IgG",

abstract = "A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligo-nucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235 → Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen.",

keywords = "Amino Acid Sequence, Animals, Binding Sites, Humans, Immunoglobulin G/metabolism, Leukocytes, Mononuclear/metabolism, Mice, Molecular Sequence Data, Protein Conformation, Receptors, Fc/metabolism, Receptors, IgG",

author = "Duncan, {Alexander R.} and Woof, {Jennifer M.} and Partridge, {Lynda J.} and Burton, {Dennis R.} and Greg Winter",

year = "1988",

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doi = "10.1038/332563a0",

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T1 - Localization of the binding site for the human high-affinity Fc receptor on IgG

AU - Duncan, Alexander R.

AU - Woof, Jennifer M.

AU - Partridge, Lynda J.

AU - Burton, Dennis R.

AU - Winter, Greg

PY - 1988/4/7

Y1 - 1988/4/7

N2 - A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligo-nucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235 → Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen.

AB - A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligo-nucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235 → Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen.

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - Humans

KW - Immunoglobulin G/metabolism

KW - Leukocytes, Mononuclear/metabolism

KW - Mice

KW - Molecular Sequence Data

KW - Protein Conformation

KW - Receptors, Fc/metabolism

KW - Receptors, IgG

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DO - 10.1038/332563a0

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JO - Nature

JF - Nature

IS - 6164

ER -

Localization of the binding site for the human high-affinity Fc receptor on IgG

Abstract

Keywords

ASJC Scopus subject areas

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