TIGIT Products

Description

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

Bioinformatics

Product By Gene ID	201633
Alternate Names	T cell immunoreceptor with Ig and ITIM domains TIGIT VSIG9 VSTM3 WUCAM

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Tired T cells: Hypoxia Drives T cell Exhaustion in the Tumor Microenvironment By Hunter MartinezThe paradigm shifting view of the immune system being leveraged to target cancer has led to numerous therapeutic breakthroughs. One major cell group responsible for this revelation is a T cell. ...    Read more.

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