DNAX accessory molecule-1 receptor (DNAM-1 (also known as CD226))

DNAX accessory molecule-1 (DNAM-1 or CD226) is an activating immunoglobulin superfamily receptor expressed predominantly on natural killer (NK) cells, CD8+ T cells, some CD4+ T cells, platelets, monocytes, dendritic cells, and hematopoietic stem cells. Structurally, it features two V-like immunoglobulin domains and a cytoplasmic domain important for downstream signaling. Its principal known ligands are CD155 (polio virus receptor, PVR, or Necl-5) and CD112 (nectin-2). Upon ligand engagement, DNAM-1 mediates cytotoxicity and cytokine production by activating signaling cascades such as phosphorylation events recruiting Grb2, which then activates Vav-1, PI3K, and PLCγ1, leading to enhanced actin polymerization, granule polarization, and target cell killing[2][3][6]. CD226-ligand interaction is crucial for immunological synapse formation, efficient tumor immunosurveillance, and responses to viral infection. Its function can be modulated by co-expressed inhibitory receptors (TIGIT, CD96), making it an attractive and actively explored immuno-oncology target[3][5][7].

Other names

CD226Platelet and T cell activation antigen 1 (PTA1)T lineage specific activation antigen 1 (TLisA1)DNAX accessory molecule-1DNAM-1

Augmentation of T and NK cell-mediated cytotoxicity via engagement with CD155 (poliovirus receptor) and CD112 (nectin-2)\n- Enhancement of immune synapse and lytic granule polarization\n- Activation of downstream kinases and adaptors (e.g., Grb2, Vav-1, PI3K, PLCγ1, ERK, AKT) following ligand binding\n- Modulation of immune cell adhesion and migration[2][3][6]