Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fcγ receptor

Gabriella Sarmay, John Lund, Zoltan Rozsnyay, Janos Gergely, Royston Jefferis

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Abstract

In the present study 3-iodo-4-hydroxy-5-nitrophenacetyl (NIP)-specific antibodies were compared for induction of antibody dependent lysis of NIP-derivatised red blood cells effected by pre-stimulated U937 or HL-60 cells and by K cells. The chimaeric antibodies have heavy chains corresponding to human IgG subclasses 1-4, and include site-directed mutants of IgG3 as well as the aglycosylated form of IgG3; a mouse IgG2b antibody and a site-directed mutant IgG2b were also examined. rIFN stimulated U937 or HL-60 cells express increased levels of Fcγ R1 compared to unstimulated cells; PMA stimulated HL-60 and U937 cells express an increased level of Fcγ R11 compared to unstimulated cells; K cells express Fcγ R111. Using these effector cell populations and the target cells mentioned above, we have compared anti-NIP antibodies with different heavy chain constant domains for their ability to induce ADCC through human Fcγ R1, Fcγ R11 and Fcγ R111. The results suggest that all three human Fcγ receptors appear to recognise a binding site on IgG within the lower hinge (residues 234-237) and trigger ADCC via this site, but that each receptor sees this common site in a different way. The possibility that other amino acid residues also participate in the binding/triggering site(s) cannot be excluded.

Original languageEnglish
Pages (from-to)633-639
Number of pages7
JournalMolecular Immunology
Volume29
Issue number5
DOIs
Publication statusPublished - 1992

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Fc Receptors
Immunoglobulin G
R 111
Antibodies
HL-60 Cells
Nitrohydroxyiodophenylacetate
Binding Sites
U937 Cells
Health Services Needs and Demand
Anti-Idiotypic Antibodies
Erythrocytes
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

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abstract = "In the present study 3-iodo-4-hydroxy-5-nitrophenacetyl (NIP)-specific antibodies were compared for induction of antibody dependent lysis of NIP-derivatised red blood cells effected by pre-stimulated U937 or HL-60 cells and by K cells. The chimaeric antibodies have heavy chains corresponding to human IgG subclasses 1-4, and include site-directed mutants of IgG3 as well as the aglycosylated form of IgG3; a mouse IgG2b antibody and a site-directed mutant IgG2b were also examined. rIFN stimulated U937 or HL-60 cells express increased levels of Fcγ R1 compared to unstimulated cells; PMA stimulated HL-60 and U937 cells express an increased level of Fcγ R11 compared to unstimulated cells; K cells express Fcγ R111. Using these effector cell populations and the target cells mentioned above, we have compared anti-NIP antibodies with different heavy chain constant domains for their ability to induce ADCC through human Fcγ R1, Fcγ R11 and Fcγ R111. The results suggest that all three human Fcγ receptors appear to recognise a binding site on IgG within the lower hinge (residues 234-237) and trigger ADCC via this site, but that each receptor sees this common site in a different way. The possibility that other amino acid residues also participate in the binding/triggering site(s) cannot be excluded.",
author = "Gabriella Sarmay and John Lund and Zoltan Rozsnyay and Janos Gergely and Royston Jefferis",
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T1 - Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fcγ receptor

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AU - Lund, John

AU - Rozsnyay, Zoltan

AU - Gergely, Janos

AU - Jefferis, Royston

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