Comparison of the ability of red cells sensitized with a bispecific anti-D x anti-Fc gamma RIII Fab fragment to activate human K cells and peritoneal macrophages through Fc gamma RIII.
The functional activity of Fc gamma RIII on human K cells from peripheral blood was compared with that of Fc gamma RIII on peritoneal macrophages (PM) separated from the waste material of patients undergoing peritoneal dialysis. Fc gamma R function was assessed in vitro using human monoclonal IgG1 anti-D (AB5) or a bispecific antibody comprising Fab fragments of AB5 chemically linked to Fab fragments of monoclonal anti-Fc gamma RIII, 3G8 (AB5 x 3G8). In antibody-dependent cell-mediated cytotoxicity (ADCC) assays, K cells mediated the lysis of papainized red cells sensitized with the AB5 x 3G8 bispecific antibody but not with AB5. In contrast, red cell lysis by PM was not promoted by AB5 x 3G8 although AB5 was active. However, this lysis, being inhibited by monomeric IgG, was presumably mediated via Fc gamma RI. AB5 x 3G8 also failed to promote the binding and phagocytosis of both papainized and native red cells by PM although 99% of red cells and over 90% of peritoneal cells bound the bispecific antibody. In marked contrast to K cells therefore, Fc gamma RIII on PM was unable to mediate functional interactions with red cells sensitized with anti-D x anti-Fc gamma RIII bispecific antibody.
Bakács
T
T
National Institute of Oncology, Budapest, Hungary.
Hadley
A G
AG
Kumpel
B M
BM
Segal
D M
DM
Banhidy
F
F
D018033:Antibodies, Bispecific / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*; D012204:Rh-Hr Blood-Group System / Q000276:immunology*
D018033:Antibodies, Bispecific; D007140:Immunoglobulin Fab Fragments; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen