Cutting edge: Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family

Some CD2 family receptors stimulate NK cell-mediated cytotoxicity through a signaling pathway, which is dependent on the recruitment of an adapter pro tein called SLAM-associated protein (SAP). In this work we identify a novel leukocyte cell surface receptor of the CD2 family called CD2-like receptor activating cytotoxic cells (CRACC). CRACC is expressed on cytotoxic lympho cytes, activated B cells, and mature dendritic cells, and activates NK cell -mediated cytotoxicity. Remarkably, although CRACC displays cytoplasmic mot ifs similar to those recruiting SAP, CRACC-mediated cytotoxicity occurs in the absence of SAP and requires activation of extracellular signal-regulate d kinases-1/2. Thus, CRACC is a unique CD2-like receptor which mediates NK cell activation through a SAP-independent extracellular signal-regulated ki nase-mediated pathway.