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.
Lopez Guerrero
J A
JA
Department of Microbiology, Centro de Biología Molecular, CSIC-UAM, Canto Blanco, Spain.
Redondo
J M
JM
Alarcón
B
B
Sánchez-Madrid
F
F
Rodríguez Moya
M
M
Ortíz de Landazuri
M
M
Bernabeu
C
C
Fresno
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D011990:Receptors, Transferrin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011990:Receptors, Transferrin