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-III

The functional activity of Fc gamma RIII on human K cells from periphe ral blood was compared with that of Fc gamma RIII on peritoneal macrop hages (PM) separated from the waste material of patients undergoing pe ritoneal dialysis. Fc gamma R function was assessed in vitro using hum an monoclonal IgG1 anti-D (AB5) or a bispecific antibody comprising Fa b fragments of AB5 chemically linked to Fab fragments of monoclonal an ti-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 wi th AB5. In contrast, red cell lysis by PM was not promoted by AB5 X 3G 8 although AB5 was active. However, this lysis, being inhibited by mon omeric IgG, was presumably mediated via Fc gamma RI. AB5 X 3G8 also fa iled to promote the binding and phagocytosis of both papainized and na tive red cells by PM although 99% of red cells and over 90% of periton eal-cells bound the bispecific antibody. In marked contrast to K cells therefore, Fc gamma RIII on PM was unable to mediate functional inter actions with red cells sensitized with anti-D X anti-Fc-gamma III bisp ecific antibody.