Blocking the interaction between CD158a, CD158b, and CD159a on NK cells and HLA-C and -E molecules on infected cells increases the ability of NK cells to destroy HIV-infected autologous primary T cells. HIV-1_SF162-infected T-cell blasts, uninfected CD4⁺ T cells, and K562 cells were used as target cells in a 4-hour cytotoxicity assay. Effector cells (NK cells) were isolated from the same donor from whom the CD4⁺ T cells were isolated and were incubated with or without 10 μg/mL purified anti-CD158a, CD158b, and CD159a antibody before addition to target cells. Effector cell-target cell ratios of 1:1, 5:1, 10:1, and 30:1 were used. All samples were performed in triplicate. The Student t test was used to determine the statistical differences between percentage of specific lysis of HIV-infected cells by NK cells in the absence or presence of anti-CD158, -CD158b, and -CD159a antibody. ^*P < .05; ^**P < .01. ND indicates not done.