Enhancement of tumor cell lysis by natural killer cells after blocking of HLA-monomorphic determinant using F(ab')2 fragment of W6/32.

Abstract

It has been known that negative signal of natural killer (NK) cells is triggered by HLA-polymorphic determinant (PMD) of target cells. However, it is not clear whether or not the negative signal is triggered by HLA-monomorphic determinant (MMD). In this study, we determined the interaction of NK receptor and MMD by mean of a blocking test. For the blocking, W6/32, which is an antibody to the MMD, was used. As target cells, we used a tumor cell line H42 and several cell lines. The H42 was established from a bladder cancer patient after radiation therapy. This cell line was demonstrated to be PMD negative but MMD positive and showed NK sensitivity. We had established one more cell line, H41, from the same patient before the radiation therapy. However, the H41 possessed both the PMD and MMD and exhibited NK resistance. Thus, the NK sensitivity of the H42 may be due to depression of the PMD. We performed a blocking test against the MMD of these cell lines. When the H42 was pretreated with F(ab')2 fragment of the W6/32, the killing by NK cells increased. Other cell lines, EB33, KMT-1, and HMy2-C1R, which possessed low levels of PMD, were killed moderately after the pretreatment, although the H41 and other cell lines (KO, MT-2, OKM-3T), which possessed high levels of PMD, were killed only slightly. These findings suggest that the negative signal may be triggered not only by the PMD but also by the MMD.