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Applications: This cell line is ideal for high throughput screening (HTS) to identify antagonistic monoclonal antibodies targeting either TIGIT or its ligands, such as CD155 in a cellular context.
Background: TIGIT is a co-inhibitory receptor that is highly expressed in Natural Killer (NK) cells, activated CD4+, CD8+ and regulatory T cells. Interaction with the poliovirus receptor (PVR; CD155) on antigen presenting cells, such as dendritic cells, recruits Src homology (SH) domain-containing protein tyrosine phosphatase SHP1 and SHP2 or the inositol phosphatase SHIP1 and SHIP2 to the TIGIT ITIM domain. This increases IL-10 release and suppresses NF-kB and NFAT T cell receptor (TCR) signaling, which blocks T cell proliferation and cytokine production. It serves as a competitive inhibitor of CD226, a co-stimulatory receptor for CD155. TIGIT targeting antibodies that block this T cell-intrinsic inhibitory effects have shown enhancedanti-tumor and anti-viral functions in preclinical studies.
Description: Recombinant Jurkat cell line constitutively expressing a full length human TIGIT (Tcell Immunoreceptor with Immunoglobulin and ITIM domain; VSTM3), and a firefly luciferasegene under the control of nuclear factor of activator T cells (NFAT) response element. BothTIGIT and NFAT constructs have been stably integrated into Jurkat cells. TIGIT expression hasbeen confirmed by Western Blot, and TIGIT-specific NFAT response has been validated using aTIGIT ligand, CD155 (PVR).
Format: Aqueous solution containing DMSO
Host Cell Line: Jurkat
Mycoplasma Testing: This cell line has been screened using the MycoAlert™ Mycoplasma Detection Kit (Lonza, Cat.#LT07-118) to confirm the absence of Mycoplasma contamination. MycoAlert Assay Control Set(Lonza, Cat. #LT07-518) was used as a positive control.
Storage Stability: Store in liquid nitrogen immediately upon receipt.
Warnings: Avoid freeze/thaw cycles.
Biosafety Level: BSL-1
References: 1. Li M et.al (2014) T-cell Immunoglobulin and ITIM Domain (TIGIT) Receptor/ Poliovirus Receptor (PVR) Ligand Engagement Suppresses Interferon-g Production of Natural Killer Cells via b-arrestin 2-mediated Negative Signaling. J Biol Chem. 289: 17647- 17657.
2. Stanietsky N. et.al. (2009) The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. PNAS. 106: 17858-17863.
3. Zhu et.al. (2016) Identification of CD112R as a novel checkpoint for human T cells. J Exp. Med. 213: 167-176.
4. Yu X. et.al. (2008) The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat.Immunol. 10: 48-57.
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