Mapping the functional topography of Fcγ with monoclonal antibodies: localization of epitopes interacting with the binding sites of Fc receptor on human K cells

Gabriella Sármay, Roy Jefferis, Eva Klein, Miklós Benczur, Janos Gergely

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

A panel of monoclonal antibodies (mAb) specific for the Cγ2, Cγ3 or inter Cγ2/Cγ3 domain epitopes was tested for inhibition of antibody‐dependent cellular cytotoxicity (ADCC) specific for anti‐D IgG‐coated erythrocytes. Significant inhibition of ADCC was demonstrable for some antibodies having specificity for Cγ2 or Cγ3 domain epitopes, while others gave no inhibition. Fab fragments of a representative Cγ2‐specific antibody (A55) and Cγ3‐specific antibody (x3a8) retained their inhibitory capacity in lymphocyte‐mediated ADCC, but only A55 Fab inhibited monocyte‐mediated lysis. Furthermore, the Fab portion of A55 completely abolished the complement‐dependent enhancement of ADCC mediated by concanavalin A‐stimulated cells, while x3a8 Fab had no effect in this system. On the other hand, x3a8 Fab inhibited the binding of anti‐D IgG‐sensitized erythrocytes to lymphocytes while A55 Fab did not influence this latter interaction. The results suggest that Cγ2 domain‐FcR interaction is essential for the triggering of lytic process both in lymphocyte and in monocyte‐mediated ADCC, while Cγ3 domain has no role in the latter but is responsible for the appropriate contact between effector lymphocytes and target cells. A site in the region of Lys274 appears to be critical for triggering of both lymphocyte and monocyte‐mediated ADCC.

Original languageEnglish
Pages (from-to)1037-1042
Number of pages6
JournalEuropean journal of immunology
Volume15
Issue number10
DOIs
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Mapping the functional topography of Fcγ with monoclonal antibodies: localization of epitopes interacting with the binding sites of Fc receptor on human K cells'. Together they form a unique fingerprint.

  • Cite this