LFA-1 and CD2 synergize for the Erk1/2 activation in the Natural Killer (NK) cell immunological synapse

Natural killer (NK) cell recognition and formation of a conjugate with target cells, followed by intracellular signal pathway activation and degradation of cytolytic granules, are essential for NK cell cytotoxicity. In this study, NK92 cells were used to investigate synapse formation and subsequent signaling after binding to the target cell. The binding rate of the NK92-target cell was associated with NK92 cell cytotoxicity. Confocal results showed that adhesion molecules, LFA-1 (CD11a) and CD2, accumulated at the interface of the NK92-K562 contact. Ligation with K562 cells activated the Erk1/2 signal pathway of NK92 cells. The blocking of the NK-target conjugate by EDTA or anti-CD11a or/and anti-CD2 antibody decreased the phosphorylation of Erk1/2 and NK cell cytotoxicity. Inhibition of Erk1/2 phosphorylation by the chemical inhibitor U0126 suppressed the cytolytic activity of NK92 cells, but had no effect on NK-target conjugate formation. Thus, conjugate formation of the NK92-target cell was prerequisite to NK cell activation, and subsequent signal transduction was also required for NK cell cytotoxicity.