Correlations between the 44D7 antigenic complex and the plasma membrane Na+–Ca2+ exchanger

The exchange of Na+ for Ca2+ across the plasma membrane is mediated by a carrier transport system known as the Na+–Ca2+ exchanger. We have recently reported the specific inhibition of Na+–Ca2+ exchanger activity in cardiac and skeletal muscle sarcolemmal vesicles by monoclonal antibody 44D7. In this review, we summarize the properties of the 44D7 monoclonal antibody and the antigenic complex reacting with this antibody. The 44D7 antibody was produced against human acute lymphocytic cells and recognizes a molecular complex composed of two subunits of the apparent molecular weights 95 000 and 38 000, linked by disulfide bonds. Two other monoclonal antibodies react with the same complex: 4F2 which binds to the same epitope as 44D7 and specifically inhibits the Na+–Ca2+ exchanger activity, and 44H7 which reacts with a distinct epitope and does not inhibit exchanger activity. The 44D7 antibody reacts with nerve fibers in brain and proximal convoluted tubules of kidney, both known to possess Na+–Ca2+ exchanger activity. Reactivity of 44D7 antibody with tonsil and thymus sections is restricted to certain subpopulations of cells. The reactivity of the antibody is very weak with resting lymphocytes in suspension; however, activated T lymphocytes and leukemic cells show increased binding to 44D7 antibody. Several malignant cell lines express high levels of the 44D7 antigen. The reactivity of a human hepatoma with 44D7 antibody is much greater than that observed with normal hepatocytes. The inhibition by monoclonal antibody 44D7 of the Na+–Ca2+ exchanger activity and the similarity in tissue distribution of the 44D7 antigenic complex and the exchanger system suggests that these two molecules might be related. Demonstration of a direct correlation between these two entities will require the isolation of a molecule expressing both antigenic and exchanger activities.