CD155 / PVR is a glycoprotein composed of two Ig-like C2-type domains and one Ig-like V-type domain that is necessary for poliovirus binding and uptake. CD155 / PVR is a broadly expressed receptor that can interact with several ligands, such as CD226 / DNAM-1, TIGIT, CD96, vitronectin, integrin αvβ3, and PDGFR. The functions of CD155 / PVR include roles in cell adhesion, neural differentiation, and NK cell effector functions.
CD226 (also known as DNAM-1) is a glycoprotein belonging to the Ig superfamily that is expressed on the surface of NK cells, platelets, monocytes, and activated CD4+ T cells. CD226 / DNAM-1 binds to CD155 / PVR and CD112, both expressed on APCs, but only CD155 / PVR is induced in T cells upon their activation. CD226 / DNAM-1 mediates cellular adhesion and triggers NK cell effector functions. In human CD4+ T cells, CD266 & CD155 immune checkpoint pathway associates with LFA-1 and contributes to LFA-1 costimulatory signals that promote Th1 cell differentiation. CD226 / DNAM-1 allelic variants have been defined as a genetic risk factor for developing MS and T1D. This disease-associated single-nucleotide polymorphism is located in the coding region and generates an amino acid change Ser307Gly in the intracellular domain. Although these genomic data identify molecules involved in autoimmunity in an unbiased manner, the functional role of CD226 / DNAM-1 in human autoimmune diseases has not been defined.
Ester Lozano et al. The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans. The Journal of Immunology. 2013; 191: 3673-3680