CD226 (Phospho-Ser329) ELISA Kit

CD226 (DNAM-1) is a molecule that has been recently given a great deal of attention due to its immunomodulatory properties and possible usefulness in assessment of tumors and autoimmune disorders activity. This cellular transmembrane activating immunoreceptor is expressed predominantly on the surface of natural killer cells, most CD4+ T cells and CD8+ T cells, platelets, and monocytes (1). CD226, also known as DNAM-1 (DNAX Accessory Molecule-1), was originally described as an adhesion molecule that controls NK cell-mediated cytotoxicity (2). CD226 is also speculated to be an important suppressor of autoimmune responses (3). Single nucleotide polymorphism (rs763361) in CD226 gene, which leads to one amino acid substitution (Gly307Ser) in CD226, was reported to be associated with the development of several autoimmune diseases, including type 1 diabetes (T1D), multiple sclerosis, autoimmune thyroid disease (AITD) and rheumatoid arthritis (RA) (3). Interestingly, we and others reported that patients with distal 18q deletion syndrome -a natural model of CD226 haploinsufficiency, seem to be at higher risk of developing autoimmune conditions including T1D, AITD or vitiligo, coexisting with antibody and T regulatory cells deficiency (4). Membrane CD226 (mCD226) expressed on peripheral blood mononuclear cells might be shed from cell membranes by certain proteases and appear in the serum in its soluble (sCD226) form (5,6). There is a substantial body of evidence showing that sCD226 affects the interaction between CD226 and its ligands, resulting in modulation of CD226-mediated immune responses (7).

Coinhibitory receptors, such as CTLA-4 and PD-1, play a critical role in maintaining immune homeostasis by dampening T cell responses. Recently, they have gained attention as therapeutic targets in chronic disease settings where their dysregulated expression contributes to suppressed immune responses. The novel coinhibitory receptor TIGIT (T cell Ig and ITIM domain) has been shown to play an important role in modulating immune responses in the context of autoimmunity and cancer. However, the molecular mechanisms by which TIGIT modulates immune responses are still insufficiently understood. We have generated a panel of monoclonal anti-mouse TIGIT Abs that show functional properties in mice in vivo and can serve as important tools to study the underlying mechanisms of TIGIT function. We have identified agonistic as well as blocking anti-TIGITAb clones that are capable of modulating T cell responses in vivo. Administration of either agonist or blocking anti-TIGIT Abs modulated autoimmune disease severity whereas administration of blocking anti-TIGIT Abs synergized with anti-PD-1 Abs to affect partial or even complete tumor regression. The Abs presented in this study can thus serve as important tools for detailed analysis of TIGIT function in different disease settings and the knowledge gained will provide valuable insight for the development of novel therapeutic approaches targeting TIGIT.