DNAX Accessory Molecule–1 (DNAM‑1)

DNAM-1, also known as CD226, is a co-activation and activating receptor primarily expressed on natural killer (NK) cells, CD8+ T cells, some subsets of CD4+ T cells, and other immune cell types such as macrophages and platelets. It plays a critical role in the regulation of immune responses including cell adhesion, lymphocyte signaling, cytokine secretion, cytotoxicity against target cells (such as tumor or virus-infected cells), and immune synapse formation. Upon engagement with its ligands—primarily CD155 (PVR) and CD112 (Nectin-2)—DNAM-1 delivers activating signals that promote NK cell-mediated killing of transformed or virus-infected target cells, cytokine production by NK and T cells, and expansion/maintenance of memory NK cell populations after viral infection. The receptor's activation enhances actin polymerization/granule polarization in effector lymphocytes to facilitate effective cytotoxic responses. DNAM‑1–ligand interactions are crucial for effective tumor surveillance. Loss or blockade impairs NK/T-cell mediated suppression of tumors/metastases; conversely, adequate expression enhances recognition/killing especially in hematologic malignancies like AML. The pathway is being explored therapeutically via engineered chimeric receptors to boost anti-tumor immunity in adoptive cell therapies.

Other names

CD226Cluster Differentiation antigen 226

Engineered chimeric receptors to boost anti-tumor immunity in adoptive cell therapies; Blockade of DNAM-1/ligand interactions