Characteristics of human T-lymphotropic virus type-1 (HTLV-1)-infected cell line MT-2, which is not killed by a natural killer cell line NK-92 but iskilled by lymphokine-activated killer cells

Natural killer (NK) cell-mediated cytolysis (NK-lysis) is triggered by cost imulatory signals of adhesion molecules and is downregulated by negative si gnals of killer cell inhibitory receptors (KIRs). Recently, a NK cell line, NK-92, was established. This cell line can kill several tumor cells, which possess adhesion molecules CD54 and CD102. However, the NK-92 cannot kill a human T-lymphotropic virus type 1 (HTLV-l)-infected cell line, MT-2, alth ough lymphokine-activated killer (LAK) cells can kill MT-2. In this report we investigated the reason for LAK sensitivity but NK-92 resistance of the MT-2. The MT-2 highly expressed CD54 and CD102, suggesting that the costimu latory signals may be intact. Then we tested the responsibility of the nega tive signals by determining HLA type of the MT-2 and KIRs of the effector c ells. The MT-2 expressed HLA-A24, B40, B51, Cw3, and HLA-G. The NK-92 did n ot express KIR2DL1, KIR2DL2,3, nor KIR3DL1, but 24% of the cells weakly exp ressed CD94. The blocking tests against these HLA class I molecules and Kms did not restore the NK-92 resistance, although blocking against HLA-G slig htly increased its lysis. Finally, in order to eliminate the class I molecu les from the cell surface, we treated the MT-2 using a buffered citric acid solution (pH 3.8). By using this treatment, the expression of class I mole cules and HTLV-1 antigen decreased, and then the MT-2 was killed by the NK- 92. These findings suggest that an aberrant class I molecule of the MT-2 tr ansferred a negative signal to the NK-92 and induced the NK-92 resistance. rt remains to be elucidated whether or not the HTLV-l infection contributed to the alteration of the class I molecule.