Ligand inhibition studies on the role of Fc receptors in antibody-dependent cell-mediated cytotoxicity

G. Sármay, M. Benczur, G. Petrányi, E. Klein, M. Kahn, D. R. Stanworth, J. Gergely

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Abstract

Subjection of human peripheral blood lymphocytes to a temp shift from 4 to 37°C resulted in a shedding of Fc receptors (termed FcRI) from 40-50% of FcR-positive cells followed by their re-expression within 4hr; a phenomenon which had no effect on the cells' antibody-dependent killing capacity. Removal of lymphocytes having an immobile form of the Fc receptor resistant to the effects of the temp shift (termed FcRII), or removal of lymphocytes bearing both FcRI and FcRII, resulted in a similar amount of reduction in ADCC activity. This was attributed, therefore, to the loss of FcRII-positive cells. The influence of isolated (shedded) FcRI and C1q on ADCC activity was investigated. Soluble FcRI was shown to inhibit ADCC mediated through the immobile Fc receptors (FcRII), despite its lack of an ability to block EA rosette formation through these receptors. C1q also had a dose-dependent inhibitory effect on ADCC. These observations are consistent with earlier findings that FcRII possesses two active binding sites; and suggest that a prerequisite for killing in ADCC is the interaction of these with the Cγ2 and Cγ3 domains. The ability of synthetic peptides representative of human γ1-chain sequences to inhibit ADCC was determined, in an attempt to locate those sites within the IgG antibody Fc region involved in interaction with two FcR binding sites. Preliminary evidence was obtained to suggest that one of these is situated within the Cγ2 domain, in the region of residues 274 (Lys)-294 (Glu).

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalMolecular Immunology
Volume21
Issue number1
DOIs
Publication statusPublished - 1984

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Antibody-Dependent Cell Cytotoxicity
Fc Receptors
Ligands
Lymphocytes
Binding Sites
Rosette Formation
Antibodies
Catalytic Domain
Immunoglobulin G
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Ligand inhibition studies on the role of Fc receptors in antibody-dependent cell-mediated cytotoxicity. / Sármay, G.; Benczur, M.; Petrányi, G.; Klein, E.; Kahn, M.; Stanworth, D. R.; Gergely, J.

In: Molecular Immunology, Vol. 21, No. 1, 1984, p. 43-51.

Research output: Contribution to journalArticle

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