ZAP-70 is required for calcium mobilization but is dispensable for mitogen-activated protein kinase (MAPK) superfamily activation induced via CD2 in human T cells

Stimulation with specific pairs of anti-CD2 antibodies can induce T cell ac tivation and proliferation. In this study, we investigate the significance of ZAP-70 in CD2 signaling using ZAP-70-deficient T cells derived from a CD 8-deficient patient and show that ZAP-70 is necessary for cellular prolifer ation and cytokine production in T cells stimulated via CD2, Biochemical an alyses show that CD2 stimulation induces activation of mitogen-activated pr otein kinase (MAPK) superfamily in ZAP-70-deficient T cells, indicating tha t a ZAP-70-independent pathway(s) exists for MAPK superfamily activation vi a CD2. In contrast, intracellular Ca2+ mobilization and activation of nucle ar factor of activated T cells (NFAT) upon CD2 triggering were impaired in T cells lacking ZAP-70. Furthermore, we found that pharmacological Ca2+ ele vation combined with CD2 stimulation restored NFAT activation and subsequen t cytokine production in ZAP-70-deficient T cells. These results indicate t hat in CD2 signaling, ZAP-70 plays an essential role in Ca2+ mobilization a nd NFAT activation.