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 (1-4). 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 site, a 21 aa transmembrane sequence, and an 82 aa cytoplasmic domain with an ITIM motif (5). A 170 aa variant diverges after aa 166 (5). Within the ECD, human TIGIT shares only 68-75% aa sequence identity with mouse, porcine, canine, equine and bovine TIGIT. Cyno TIGIT shares 88.4% homology with human TIGIT. TIGIT is expressed on NK cells and subsets of activated, memory and regulatory T cells, and particularly on follicular helper T cells within secondary lymphoid organs (1, 2, 6-8). It binds to CD155/PVR/Necl-5 and Nectin-2/CD112/PVRL2 that appear on dendritic cells (DC) and endothelium (1-3, 7). Binding of TIGIT by DC induces IL-10 release and inhibits IL-12 production (2). Ligation of TIGIT on T cells down‑regulates TCR-mediated activation and subsequent proliferation, while NK cell TIGIT ligation blocks NK cell cytotoxicity (6-8). Through CD155 and Nectin-2, which also interact with DNAM-1/CD226 and CD96/Tactile, TIGIT is part of an interacting network of Ig superfamily members that may augment or oppose each other (3, 4, 6, 7). In particular, TIGIT binding to CD155 can antagonize the effects of DNAM-1 (6, 7). Soluble TIGIT is able to compete with DNAM-1 for CD155 binding and attenuates T cell responses, while mice lacking TIGIT show increased T cell responses and susceptibility to autoimmune challenges (2, 3, 8).

References

Boles, K.S. et al. (2009) Eur. J. Immunol. 39:695.
Yu, X. et al. (2009) Nat. Immunol. 10:48.
Levin, S.D. et al. (2011) Eur. J. Immunol. 41:902.
Xu, Z. et al. (2010) Cell. Mol. Immunol. 7:11.
SwissProt Accession # Q495A1.
Seth, S. et al. (2009) Eur. J. Immunol. 39:3160.
Stanietsky, N. et al. (2009) Proc. Natl. Acad. Sci. USA 106:17858.
Joller, N. et al. (2011) J. Immunol. 83:1338.

Long Name

T Cell Immunoreceptor with Ig and ITIM Domains

Alternate Names

VSIG9, VSTM3, WUCAM

Entrez Gene IDs

201633 (Human); 100043314 (Mouse); 363784 (Rat); 102121588 (Cynomolgus Monkey)

Gene Symbol

TIGIT

UniProt

XP_00554815

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This product is provided under an intellectual property license from Life Technologies Corporation. The transfer of this product is conditioned on the buyer using the purchased product solely in research conducted by the buyer, excluding contract research or any fee for service research, and the buyer must not (1) use this product or its components for (a) diagnostic, therapeutic or prophylactic purposes; (b) testing, analysis or screening services, or information in return for compensation on a per-test basis; or (c) manufacturing or quality assurance or quality control, and/or (2) sell or transfer this product or its components for resale, whether or not 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, 5781 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@thermofisher.com.

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Cynomolgus Monkey TIGIT Alexa Fluor™ Plus 405-conjugated Antibody

R&D Systems, part of Bio-Techne | Catalog # FAB10532AFP405

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Blockade of Receptor-ligand Interaction

CyTOF-ready

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Background: TIGIT