CD226 antigen (CD226) (CD226)

CD226, also known as DNAX accessory molecule 1 (DNAM-1), is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily (UniProt P43489). It is constitutively expressed on the surface of natural killer (NK) cells, T cells, monocytes, and platelets, where it functions as a crucial activating receptor and adhesion molecule (PubMed: 15905536). CD226 mediates cellular adhesion and triggers effector functions by binding to its ligands, CD155 (PVR) and CD112 (Nectin-2), which are frequently overexpressed on various cancer cells and antigen-presenting cells (NCBI Gene ID: 10666). In the context of oncology, CD226 is a key player in immune surveillance, as its activation promotes the lysis of tumor cells; however, its expression is often downregulated in the tumor microenvironment, contributing to immune evasion (PubMed: 29061859). Consequently, CD226 is a significant target for cancer immunotherapy, with agonistic antibodies like Etigalimab being developed to restore or enhance its signaling (ClinicalTrials.gov: NCT03665285). Beyond cancer, genetic polymorphisms in the CD226 gene are strongly associated with susceptibility to several autoimmune diseases, including rheumatoid arthritis and type 1 diabetes, making it a target for inhibitory strategies to dampen overactive immune responses (PubMed: 19633202).

Other names

DNAM-1DNAX accessory molecule 1PTA1TLiSA1Platelet and T cell activation antigen 1

Agonism of CD226 enhances the activation and cytotoxicity of Natural Killer (NK) cells and CD8+ T cells against tumor cells by promoting signaling through the CD226-CD155/CD112 axis (PubMed: 29061859). Conversely, antagonism or blockade of CD226 is explored to reduce pathological immune activation in autoimmune and inflammatory conditions (PubMed: 19633202).