Localization of Pepstatin's inhibitory action during Fc-mediated antibody internalization: Possible implications for antibody-mediated viral transmission

Antibody internalization via Fc receptors is an important cellular mechanis m, possibly facilitating the entry of antigenic peptides or viral particles into cells when specific antibodies are present at the periphery. Using an experimental model of trophoblast cells, we have shown that anti-p21(ras) monoclonal antibodies can use IFN-gamma-induced surface Fc gamma receptors to enter the cell. This entry of anti-p21(ras) antibodies ultimately inhibi ts IFN-gamma-mediated class II antigen induction. Since there may be obviou s and inevitable harmful aspects of this mechanism, during which Fc-mediate d viral particle or autoantigen transport may occur, we concentrated effort s on defining a potent inhibitor able to eliminate such uptake. The results presented here show that the protease inhibitor pepstatin A efficiently in hibits Fc gamma receptor induction by IFN-gamma and also blocks the endocyt ic pathway followed by an antibody when it enters the cell at the level of early endosomal compartments. We thus postulate that the use of pepstatin A , because of its inhibition of autoantigen presentation or viral transmissi on, including that of HDV, may find important applications in therapeutic p rotocols. (C) 2000 Academic Press.