DNAM-1/CD226 Immune Checkpoint Molecule for Drug Development

Immune Checkpoint DNAM-1/CD226

DNAX Accessory Molecule-1 (DNAM-1), also known as Cluster of Differentiation 226 (CD226), is a kind of adhesion molecule expressed in a wide range of cells, including natural killer (NK) cells, NK T cells, T cells, a subset of B cells, dendritic cells, hematopoietic precursor cells, platelets, and monocytes.

CHECKPOINT RECEPTOR	DNAX-1
ALTERNATE NAME	CD226, PTA-1(outdated)
CELL TYPE AFFECTED	NK cells, T cells, B cells, NK T cells, dendritic cells, hematopoietic precursor cells, platelets, monocytes, etc.
MAIN LIGAND	CD112, CD155,
THE FUNCTION OF LIGAND-RECEPTOR INTERACTION	Co-stimulation

Structure of DNAM-1/CD226

DNAM-1/CD226 is a ~65 kDa immunoglobulin-like transmembrane glycoprotein, which is a member of the immunoglobulin (Ig) superfamily. It consists of 1) two extracellular Ig-like domains CD226-D1 and CD226-D2) of the V set, 2) a transmembrane domain of 28 aa, 3) eight N-glycosylation sites, and 4) a 60 aa cytoplasmic domain with three putative sites of phosphorylation by intracellular kinases.

Functions of DNAM-1/CD226

DNAM-1/CD226 is the only stimulatory receptor in the Ig superfamily. Since there is no tyrosine-based activation motif (which is recognized as essential for activating signal transduction of stimulatory molecules) in the intracellular domain of DNAM-1/CD226, it performs downstream signal transduction by phosphorylation of intracellular phosphorylation sites and association with integrin lymphocyte function-associated antigen. DNAM-1/CD226 plays broad roles in cellular adhesion, and regulation of NK cell functions. It is also reported to be involved in the crosstalk between T lymphocytes and NK cells, lysing activated T lymphocytes in graft versus host disease. Additionally, it is demonstrated that DNAM-1/CD226 can improve NK and T cell-mediated cytotoxicity against virus-infected cells and certain tumors.

DNAM-1/CD226 Immune Checkpoint Molecule for Drug Development

Different from all the known inhibitory Ig-like molecules, the unique mechanism and potential in predicting prognosis and immunotherapy response of DNAM-1/CD226 has drawn great interest. As induction of the expression of DNAM-1 and its ligand provides a prospective strategy for immune checkpoint drug development, many preclinical trials are currently being performed.

Services at Creative Biolabs

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