TIGIT (T cell Immunoreceptor with Ig and ITIM domains), also called Vstm3 (V-set and transmembrane domain-containing 3), Vsig9 (V-set and Ig domain-containing 9) and WUCAM (Washington University cell adhesion molecule), is a 30-34 kDa type I transmembrane protein that is a member of the CD28 family within the Ig superfamily of proteins (1-3). Human TIGIT cDNA encodes 244 amino acids (aa) including a 21 aa signal sequence, a 120 aa extracellular region with a V-type Ig-like domain and two potential N-glycosylation sites, a 21 aa transmembrane sequence, an 82 aa cytoplasmic domain with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and has a theoretical molecular weight of ~27 kDa (3). TIGIT is expressed as a homodimer receptor on NK cells and subsets of activated, memory and regulatory T (Treg) cells, and on follicular helper T cells within secondary lymphoid organs (4). TIGIT has three known homodimer ligands that belong to the nectin family that are expressed on antigen presenting cells (APCs) or tumor cells (5). CD155 is the primary ligand for TIGIT, but it is also capable of binding CD112 and CD113 (5). The CD155/TIGIT signaling axis is an emerging immune checkpoint that inhibits function of T cells and NK cells. Upon TIGIT ligation, CD155 signaling leads to increased secretion of interleukin 10 (IL-10) and decreased secretion of proinflammatory cytokine IL-12 (5). TIGIT is a promising target for cancer immunotherapy and is the center of many pre-clinical studies investigating checkpoint blockade utilizing monoclonal antibodies either as a monotherapy or combination therapy (5).

TIGIT is commonly used as a marker for T cell exhaustion and its expression correlates with disease progression. Furthermore, in viral infections including HIV and SIV, TIGIT serves as a target for immune restoration (6). In cancer detection, TIGIT is upregulated and coexpressed with programmed cell death protein 1 (PD-1) on the majority of circulating tumor antigen (TA)-specific CD8+ T cells (7). In addition to this, TIGIT can inhibit immune cells at multiple steps within the cancer immunity cycle. These include inhibiting NK cell effector function, suppressing dendritic cell costimulatory abilities, suppressing CD8+ T cell effector function by Tregs or polio virus receptor (PVR)-stimulated myeloid cells, and by directly inhibiting CD8+ T cells and preventing elimination of cancer cells (7).

References

1. Joller, N., & Kuchroo, V. K. (2017). Tim-3, Lag-3, and TIGIT. Current topics in microbiology and immunology, 410, 127-156. https://doi.org/10.1007/82_2017_62

2. Xu, Z., Jin, B. A novel interface consisting of homologous immunoglobulin superfamily members with multiple functions. Cell Mol Immunol 7, 11-19 (2010). https://doi.org/10.1038/cmi.2009.108

3. Uniprot(P86176

4. Khan, M., Arooj, S., & Wang, H. (2020). NK Cell-Based Immune Checkpoint Inhibition. Frontiers in immunology, 11, 167. https://doi.org/10.3389/fimmu.2020.00167

5. Harjunpaa, H., & Guillerey, C. (2020). TIGIT as an emerging immune checkpoint. Clinical and experimental immunology, 200(2), 108-119. https://doi.org/10.1111/cei.13407

6. Blake, S. J., Dougall, W. C., Miles, J. J., Teng, M. W., & Smyth, M. J. (2016). Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. Clinical cancer research: an official journal of the American Association for Cancer Research, 22(21), 5183-5188. https://doi.org/10.1158/1078-0432.CCR-16-0933

7. Manieri, N. A., Chiang, E. Y., & Grogan, J. L. (2017). TIGIT: A Key Inhibitor of the Cancer Immunity Cycle. Trends in immunology, 38(1), 20-28. https://doi.org/10.1016/j.it.2016.10.002

Long Name

T Cell Immunoreceptor with Ig and ITIM Domains

Alternate Names

VSIG9, VSTM3, WUCAM

Gene Symbol

Tigit

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Product Specific Notices for TIGIT Antibody (741182) [Alexa Fluor® 532]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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TIGIT Antibody (741182) [Alexa Fluor® 532]

Novus Biologicals, part of Bio-Techne | Catalog # FAB7898X

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Background: TIGIT