Different functional domains on the transferrin receptor molecule defined by monoclonal antibodies.

Three monoclonal antibodies (mAb) FG 1/5, FG 1/6 and FG 2/12, specific for the human transferrin receptor molecule (TR), have been used to define epitopes on the TR molecule and to block natural killer lysis. FG 2/12 mAb but not FG 1/5 or FG 1/6 blocked [125I-] transferrin binding to the cellular receptor. Furthermore, FG 1/5 and FG 1/6 mAbs competed out the binding of each other to the cells but not significantly that of FG 2/12. As expected, the binding of F2/12 but not of FG 1/5 or FG 1/6 was inhibited by transferrin. In addition, FG 2/12 inhibited in a dose-dependent manner the NK activity of purified T3- large granular lymphocyte effector cells against HeLa or Molt-4 cells but not against K-562 or U937 cells. FG 1/5 preferentially inhibited NK activity against HeLa cells and FG 1/6 mAb was completely uneffective. These inhibitions were stronger at low effector to target cell (E:T) ratios than at high E:T ratios, suggesting that NK cells and anti-TR mAbs compete for the same site in the target cell. It was shown that FG 1/5 and FG 2/12 mAbs blocked cells' conjugate formation by acting at the target cell level. Our results confirm the role of TR as a one of the target structures in NK lysis and suggest that the epitope recognized by NK cells is close to but different from the transferrin binding site.