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

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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 languageEnglish
Pages (from-to)2657-2662
Number of pages6
JournalJournal of Immunology
Volume147
Issue number8
Publication statusPublished - 15 Oct 1991

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IgG Receptors
Immunoglobulin G
Mutation
Superoxides
Antibodies

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Lund, J., Winter, G., Jones, P. T., Pound, J. D., Tanaka, T., Walker, M. R., ... Woof, J. M. (1991). Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. Journal of Immunology, 147(8), 2657-2662.
Lund, John ; Winter, Greg ; Jones, Peter T. ; Pound, John D. ; Tanaka, Toshiyuki ; Walker, Matthew R. ; Artymiuk, Peter J. ; Arata, Yogi ; Burton, Dennis R. ; Jefferis, Royston ; Woof, Jennifer M. / Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. In: Journal of Immunology. 1991 ; Vol. 147, No. 8. pp. 2657-2662.
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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.}",
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Lund, J, Winter, G, Jones, PT, Pound, JD, Tanaka, T, Walker, MR, Artymiuk, PJ, Arata, Y, Burton, DR, Jefferis, R & Woof, JM 1991, 'Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG', Journal of Immunology, vol. 147, no. 8, pp. 2657-2662.

Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. / Lund, John; Winter, Greg; Jones, Peter T.; Pound, John D.; Tanaka, Toshiyuki; Walker, Matthew R.; Artymiuk, Peter J.; Arata, Yogi; Burton, Dennis R.; Jefferis, Royston; Woof, Jennifer M.

In: Journal of Immunology, Vol. 147, No. 8, 15.10.1991, p. 2657-2662.

Research output: Contribution to journalArticle

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AU - Winter, Greg

AU - Jones, Peter T.

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AU - Walker, Matthew R.

AU - Artymiuk, Peter J.

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AU - Burton, Dennis R.

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AU - Woof, Jennifer M.

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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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Lund J, Winter G, Jones PT, Pound JD, Tanaka T, Walker MR et al. Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. Journal of Immunology. 1991 Oct 15;147(8):2657-2662.