Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG

John Lund; Greg Winter; Peter T. Jones; John D. Pound; Toshiyuki Tanaka; Matthew R. Walker; Peter J. Artymiuk; Yogi Arata; Dennis R. Burton; Royston Jefferis; Jennifer M. Woof

Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG

John Lund, Greg Winter, Peter T. Jones, John D. Pound, Toshiyuki Tanaka, Matthew R. Walker, Peter J. Artymiuk, Yogi Arata, Dennis R. Burton, Royston Jefferis, Jennifer M. Woof

DArcy Thompson Unit

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

166 Citations (Scopus)

Abstract

Cellular receptors for IgG (FcγR) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human FcγRI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates FcγRI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in FcγRI recognition. We have also mapped an interaction site for FcγRII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in FcγRII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human FcγRI and FcγRII.

Original language	English
Pages (from-to)	2657-2662
Number of pages	6
Journal	Journal of Immunology
Volume	147
Issue number	8
Publication status	Published - 15 Oct 1991

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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https://www.jimmunol.org/content/147/8/2657

Cite this

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title = "Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG",

abstract = "Cellular receptors for IgG (FcγR) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human FcγRI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates FcγRI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in FcγRI recognition. We have also mapped an interaction site for FcγRII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in FcγRII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human FcγRI and FcγRII.",

author = "John Lund and Greg Winter and Jones, {Peter T.} and Pound, {John D.} and Toshiyuki Tanaka and Walker, {Matthew R.} and Artymiuk, {Peter J.} and Yogi Arata and Burton, {Dennis R.} and Royston Jefferis and Woof, {Jennifer M.}",

year = "1991",

month = oct,

day = "15",

language = "English",

volume = "147",

pages = "2657--2662",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

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TY - JOUR

T1 - Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG

AU - Lund, John

AU - Winter, Greg

AU - Jones, Peter T.

AU - Pound, John D.

AU - Tanaka, Toshiyuki

AU - Walker, Matthew R.

AU - Artymiuk, Peter J.

AU - Arata, Yogi

AU - Burton, Dennis R.

AU - Jefferis, Royston

AU - Woof, Jennifer M.

PY - 1991/10/15

Y1 - 1991/10/15

N2 - Cellular receptors for IgG (FcγR) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human FcγRI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates FcγRI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in FcγRI recognition. We have also mapped an interaction site for FcγRII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in FcγRII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human FcγRI and FcγRII.

AB - Cellular receptors for IgG (FcγR) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human FcγRI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates FcγRI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in FcγRI recognition. We have also mapped an interaction site for FcγRII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in FcγRII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human FcγRI and FcγRII.

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M3 - Article

C2 - 1833457

AN - SCOPUS:0026050344

SN - 0022-1767

VL - 147

SP - 2657

EP - 2662

JO - Journal of Immunology

JF - Journal of Immunology

IS - 8

ER -

Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG

Abstract

ASJC Scopus subject areas

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