Antibodies to human major histocompatibility complex products inhibit Fc gamma receptors types I and II.

We have analysed the effect of polyclonal and monoclonal antibodies of distinct IgG isotypes directed against products of the human major histocompatibility complex (MHC) on the function of Fc gamma receptors types I (Fc gamma RI) and II (Fc gamma RII). Human anti-D sensitized red blood cells (RBC), selectively binding to Fc gamma RI, and bovine or murine IgG1 (bIgG1 or mIgG1) sensitized RBC, selectively binding to Fc gamma RII, were employed as targets for the effector cell in order to distinguish the inhibition of both types. Using these targets it could be shown that human antibodies to products of the human MHC or murine monoclonal antibodies with the same specificity and mIgG2a isotype inhibited both the Fc gamma RI-and the Fc gamma RII-mediated function. In contrast, murine monoclonal antibodies with the same specificity but of the mIgG1 isotype only inhibited the Fc gamma RII-mediated function. In a control experiment, human and murine antibodies to products of the MHC did not impair the Fc gamma R-independent phagocytosis of Saccharomyces by monocytes and neutrophils. The present study suggests that this mechanism involves at least two different Fc gamma receptors.