DNAX accessory molecule 1 (DNAM-1)

DNAX accessory molecule 1 (DNAM-1), also known as CD226, is a 65 kDa type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. It is primarily expressed on the surface of natural killer (NK) cells, T cells, monocytes, and platelets, where it serves as a critical co-stimulatory receptor and adhesion molecule. DNAM-1 interacts with its ligands, CD155 (poliovirus receptor) and CD112 (nectin-2), which are frequently upregulated on the surface of tumor and virus-infected cells. This interaction triggers signaling pathways through motifs in its cytoplasmic tail, enhancing immune cell activation, cytotoxic activity, and the production of pro-inflammatory cytokines such as IFN-gamma. In the tumor microenvironment, the activity of DNAM-1 is often suppressed by competitive inhibitory receptors like TIGIT, making it a major focus for immuno-oncology therapies designed to restore immune surveillance. Conversely, overactivation of the DNAM-1 pathway contributes to pathogenic inflammation in autoimmune diseases such as multiple sclerosis and ulcerative colitis, leading to the development of neutralizing antibodies for therapeutic use. Because DNAM-1 is also expressed on platelets, its modulation carries potential risks related to platelet aggregation and vascular adhesion.

Other names

CD226PTA1TLiSA1CD226 antigenPlatelet and T cell activation antigen 1T lineage-specific activation antigen 1DNAX accessory molecule-1

Agonism, Antagonism