Identification of an evolutionarily conserved, function-associated molecule on human natural killer cells.

Nonspecific cytotoxic cells (NCC) in teleost fish are analogous to human natural killer (NK) cells and spontaneously lyse a variety of transformed human cell lines sensitive to human NK cell lysis. Monoclonal antibodies (mAbs) made against these NK-like effector cells inhibited their lytic activity. These anti-NCC mAbs were examined with human NK cells for their effects. It was observed that these mAbs bound specifically to a small percentage of peripheral blood lymphocytes (5-15%) and to the majority (greater than 85%) of CD3- NK cells. The mAbs inhibited human NK cell lysis against a variety of transformed cell lines. Single-cell assays showed that the mAbs exerted their effects through inhibition of conjugate formation (recognition). However, the mAbs did not inhibit NK cell-mediated antibody-dependent cell-mediated cytotoxicity. Biochemical analysis of the NK cell molecule revealed that a dimeric structure was involved (distinct from antigen receptors on T cells). Thus, this molecule appears to be a candidate NK cell antigen receptor.