TIGIT – CD155 – CD112 – CD226 Network

T Cell Immunoreceptor with Immunoglobulin and ITIM domains (TIGIT) is an immune checkpoint receptor expressed on the surface of cytotoxic, memory and regulatory T cells (Tregs) as well as natural killer (NK) cells. TIGIT binds strongly to CD155 (PVR) and weakly to CD112 (Nectin-2). TIGIT suppresses immune activation on cytotoxic T cells and NK cells. In the normal immune system, the suppressive effect of TIGIT is counterbalanced by the immune-activating receptor CD226 (DNAM1), which competes with TIGIT to bind CD155 and CD112. The inhibitory signal provided by TIGIT overpowers the ability of CD226 to stimulate T cell activation. Tumor cells exploit the dominance of the inhibitory TIGIT pathway to avoid immune-mediated destruction. Recently, a high affinity receptor of the ligand CD112/Nectin-2, called CD112R/PVRIG has been described and may become a new attractive cancer immunotherapy target.

LIT:  Identification of CD112R as a novel checkpoint for human T cells: Y. Zhu, et al.; J. Exp. Med. 213, 167 (2016) • Interaction of PVR/PVRL2 with TIGIT/DNAM-1 as a novel immune checkpoint axis and therapeutic target in cancer: H. Stamm, et al.; Mamm. Genome 29, 694 (2018)

Biologically Active TIGIT, CD112R and CD155 Proteins  

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