CD226 antigen (DNAM-1) (CD226)

CD226 antigen, commonly known as DNAX accessory molecule-1 (DNAM-1), is a 65 kDa type I transmembrane glycoprotein and a member of the immunoglobulin superfamily [UniProt Q15762]. It is expressed on the surface of natural killer (NK) cells, T cells, and monocytes, where it serves as a critical activating receptor that promotes cellular adhesion and triggers effector functions [PubMed: 32066598]. CD226 mediates these responses by binding to its ligands, Poliovirus Receptor (PVR/CD155) and Nectin-2 (CD112), which are frequently upregulated on tumor cells and virus-infected cells [PubMed: 28930661]. In the tumor microenvironment, CD226 competes for these ligands with inhibitory receptors such as TIGIT and CD96; because TIGIT has a significantly higher affinity for PVR, it can dominant-negatively regulate CD226-mediated activation, leading to immune exhaustion [PubMed: 25465820]. Therapeutic strategies in oncology often utilize TIGIT-blocking antibodies to restore CD226 signaling, while direct CD226 antagonists like LY3435154 are being investigated for the treatment of autoimmune and inflammatory disorders [ClinicalTrials.gov NCT05086965].

Other names

DNAM-1DNAX accessory molecule-1PTA1TLiSA1CD226

Restoration of CD226-mediated costimulatory signaling via TIGIT blockade; direct antagonism of CD226 to suppress lymphocyte activation in autoimmune contexts.