DNAX accessory molecule 1 (CD226) and its ligands (CD155 and CD112) (DNAM-1)

DNAX accessory molecule 1 (DNAM-1), also known as CD226, is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily that is expressed on the surface of natural killer (NK) cells, T cells, and monocytes [PMID: 32814716]. It serves as a critical activating receptor that mediates cellular adhesion and triggers cytotoxicity and cytokine production upon binding to its ligands, CD155 (PVR) and CD112 (Nectin-2), which are often overexpressed on tumor cells [PMID: 29109600]. In the context of the "PVR-nectin" axis, DNAM-1 competes with inhibitory receptors such as TIGIT and PVRIG for the same ligands; the balance between these signals determines the magnitude of the immune response [PMID: 31004047]. Therapeutic strategies in oncology focus on blocking these inhibitory counterparts to favor DNAM-1-mediated activation, thereby enhancing anti-tumor immunity [PMID: 34513518]. Additionally, DNAM-1 is involved in the pathogenesis of various autoimmune and inflammatory diseases, where its signaling can promote tissue-damaging immune responses [PMID: 25637016].

Other names

CD226PTA1TLiSA1DNAM1Poliovirus receptor (CD155)Nectin-2 (CD112)Necl-5 (CD155)PVR (CD155)

Restoration of DNAM-1-mediated costimulatory signaling by blocking competitive inhibitory receptors (TIGIT, PVRIG) or direct ligand interaction to enhance NK and T cell effector functions [PMID: 34513518].