Specificity of Natural Killer Cells

Natural killer (NK) l cells are unique in the lymphoid system because there is no H2 restriction of killing (1-3), no classical immunological memory, and these cells kill a wide range of unrelated target cells of both tumor (4) and non tumor origin (5). More important ly, however, N K cells pre-exist at high levels in the host (6) in contrast to other effector mechanisms (T cells, ant ibody-dependent cell-mediated cytolysis and macrophages) which require days or weeks to be primed. N K cells, therefore, might be expected to provide a first line of defence against newly arising malignancies and it was important to investigate the specificity of the target-effector interaction in this system because little is known regarding the nature of the recognition structure or the target sites involved. It is possible that the receptors are coded by the immunoglobul in variable region genes or perhaps they represent remnants of a more primitive surveillance mechanism. Previous work has shown that various unlabeled competi tor cells could inhibit isotope release from labeled target cells in a cytolytic assay and this observation was used to infer that the target and compet i tor shared common determinants which were recognized by surface receptors on the N K cell (1, 2). To directly visualize targeteffector recognition and binding, we have devised a target b inding cell (TBC) assay which detects individual N K cells (6, 7). The recognition receptor on the N K cell appears to be coded for by genes linked to the H-2 complex (6). In a previous report we showed that preincubat ion of effector cells with glycoproteins isolated from the surface of various tumor cells, selectively bound to N K cells and specifically inhibited their a t tachment to the homologous intact target cell (8). These molecules, designated natural killer cell target structure (NK-TS), were not detected on NK-insensitive targets and had no effect on a l lo immune T-cell b inding to H-2 specific targets. To extend the NK-specificity studies, we have isolated NK-TS from a number of divergent tumor cell lines and performed extensive cross-inhibition