Recognition of abnormal self on tumor or viral infected cells triggers a number of non MHC I-restricted activating receptors such as NKG2D, the receptor for the human MHC I-related sequence A and B (MICA/B) and UL16 binding proteins (ULBPs), DNAX accessory molecule-1 (DNAM-1) that recognizes nectin-2 (Nec2, CD112) and nectin-15 (Necl5, PVR, CD155), and the natural citotoxicity receptors (NCR) receptors (1). The gene discussed is CD226; the disease is neoplasm.