Antibody dependent cellular cytotoxicity (ADCC) against human erythrocytes, mediated by blood group alloantibodies: a model for the role of antigen density in target cell lysis.

Antibody dependent cellular cytotoxicity (ADCC) of human mononuclear cells against human erythrocytes could be obtained with anti-A and anti-D sera. The degree of lysis varied considerably depending on the antigen system and on the experimental conditions. Anti-D mediated in contrast to anti-A mediated ADCC turned out to be very sensitive to conditions which interfere with target cell lysis: for most of the anti-D sera, removal of unbound IgG was found to be crucial to detect their ability to mediate ADCC. Pretreatment of the target cells with various enzymes dramatically improved specific lysis and left spontaneous release and spontaneous cytotoxicity essentially unaffected. In the case of neuraminidase treatment it could be shown that the effect was independent from the exposure of additional binding sites. When enzyme treatment and removal of excess IgG were applied in combination, as little as 10(4) antigenic determinants proved to be sufficient to induce specific lysis.