DNAX accessory molecule 1 (DNAM-1) (DNAM-1)

DNAX accessory molecule 1 (DNAM-1), also known as CD226, is a pivotal activating receptor primarily expressed on natural killer (NK) cells, CD8+ cytotoxic T cells, monocytes, and platelets (UniProt, NCBI). As a type I transmembrane glycoprotein within the immunoglobulin superfamily, it plays a critical role in mediating intercellular adhesion and triggering signaling pathways that drive cytotoxicity and cytokine production (NCBI, PubMed). DNAM-1 specifically interacts with its ligands CD155 (PVR) and CD112 (Nectin-2), which are frequently overexpressed on transformed or stressed cells, such as those found in various malignancies (PMC, Frontiers in Immunology). This receptor serves as a central player in the DNAM-1/TIGIT axis, where it competitively binds these ligands to promote immune activation against tumors and pathogens. In disease states, the downregulation or loss of DNAM-1 is a known mechanism of tumor immune escape, contributing to disease progression in cancers like leukemia and melanoma (NIH, PubMed). Conversely, genetic polymorphisms and altered signaling of CD226 are strongly associated with autoimmune conditions, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus (PubMed). Therapeutic efforts involve the development of agonistic antibodies to boost anti-tumor immunity and antagonistic agents to suppress pathological immune activation in autoimmunity or graft-versus-host disease (NCBI, NCI). Additionally, much of the current clinical focus involves blocking competing inhibitory receptors like TIGIT to indirectly restore and enhance DNAM-1-mediated immune surveillance in cancer patients (Cancer Discovery).

Other names

CD226CD226 antigenT-lineage-specific activation antigen 1TLiSA1Platelet and T cell activation antigen 1PTA1Adhesion glycoproteinDNAM1

Direct agonism of the receptor to promote natural killer cell and T cell activation for cancer immunotherapy, or antagonism to inhibit excessive immune activation in autoimmune and inflammatory diseases.