CD2 is functionally linked to the zeta-natural killer receptor complex

Natural killer (NK) cells express two distinct surface receptors capable of triggering cytolytic effector function. The first is CD16, an immunoglobulin Fc receptor that allows NK cells to mediate antibody-dependent killing (ADCC). NK cells express CD16 in association with zeta, a signal-transducing subunit that is also a component of the T cell receptor complex. Activation of NK cells via CD16 results in tyrosine phosphorylation of zeta. The second NK cell triggering receptor is CD2, a 50-55-kDa cell surface molecule that is also expressed on T cells. Here we show that NK cell activation induced by mAb reactive with CD2 (either anti-T11.1 alone or with anti-T11.2 in combination) also results in the tyrosine phosphorylation of zeta. Our results indicate that CD2 is functionally linked to the CD16-zeta complex and suggest that the zeta subunit plays a central role in the signal transduction pathways utilized by NK cells.