A calmodulin antagonist increases the apparent rate of endocytosis of liposomes bound to MHC molecules via monoclonal antibodies.

We have investigated the molecular mechanisms required for endocytosis of MHC-encoded proteins by a cell line, TRH 42, that expresses endogenous murine and introduced human class I molecules. As probes we have used protein A-bearing liposomes which bind to cell surface determinants via monoclonal antibodies. The technique of fluorescence quenching release was used with liposome encapsulated quenched carboxyfluorescein as the marker for endocytosis. We demonstrate that the calmodulin antagonist trifluoperazine (TFP) enhances the apparent rate of endocytosis of liposomes bound to MHC class I molecules. Drugs that interfere with energy metabolism, microfilament organization, or phospholipase A2 activity all block endocytosis both in the presence and absence of TFP. The requirement of extracellular Ca2+ for endocytosis was found to be partial. The implications for the structural and enzymatic requirements of endocytosis of MHC class I molecules are discussed.