P46, A NOVEL NATURAL-KILLER CELL-SPECIFIC SURFACE-MOLECULE THAT MEDIATES CELL ACTIVATION

Limited information is available on the surface molecules that are inv olved in natural killer (NK) cell triggering. In this study, we select ed the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK c ell-specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigen s identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+](i) increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. T he p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibito ry receptors including p58, p70, and CD94/NKG2A. Both the unique cellu lar distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility comple x-restricted cytolysis mediated by human NK cells.