Involvement of NKR‐P2/NKG2D in DC‐mediated killing of tumor targets: indicative of a common, innate, target‐recognition paradigm?

DC are the most efficient antigen‐presenting cells that regulate the immune response. Here, we demonstrate the expression of NK cell receptor protein‐2 (NKR‐P2) on rat and mouse DC, and we show that NKR‐P2 gets reorganized upon antigen contact. DC activated with anti‐NKR‐P2 mAb exhibit enhanced apoptotic killing of tumor targets, whereas blocking the interaction between NKR‐P2 and its ligand with rNKR‐P2 abrogated apoptotic killing, suggesting NKR‐P2 to function as an activating molecule on DC. In vivo injection of anti‐NKR‐P2 mAb augmented DC activity and delayed tumor progression. NKR‐P2 signaling involved Ca2+ influx, culminating in the expression of the apoptosis‐inducing molecule, TNF‐α. Taken together, these observations suggest that NKR‐P2 (the rat orthologue of human NKG2D) acts as a target‐recognition molecule on DC.