ArticleThe Journal of biological chemistry2017
Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT).
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 101 citations in OpenAlex.
- The role of adhesins ofGut microbes · 2026Review
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- Spatial and functional specialization of human splenic innate lymphoid cells.Nature communications · 2026Article
- scComm: a contrastive learning framework for deciphering cell-cell communications at single-cell resolution.Genome biology · 2026Article
- Regulation of natural killer cell infiltration and tumor progression by CMTM6 in gastric cancer.BMC cancer · 2026Article
- Kangayam and Tharparkar cattle exhibit higher duplications in innate immune genes compared to Sahiwal, Gir, Karan Fries, and Holstein Friesian: insights from an array comparative genomic hybridization.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Structural basis of Fusobacterium nucleatum adhesin Fap2 interaction with receptors on cancer and immune cells.Nature communications · 2025Article
- Pharmacological and structural characterization of vibostolimab, a novel anti-TIGIT blocking antibody for cancer immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Structure-guided engineering of CD112 receptor variants for optimized immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- ST6GalNAc-I regulates tumor cell sialylation via NECTIN2/MUC5AC-mediated immunosuppression and angiogenesis in non-small cell lung cancer.The Journal of clinical investigation · 2025Article
- The homeostasis and heterogeneity of regulatory T cells in sepsis.Burns & trauma · 2025Article
- AI-enhanced profiling of phage-display-identified anti-TIM3 and anti-TIGIT novel antibodies.Frontiers in immunology · 2025Article
- Recognition of Self and Viral Ligands by NK Cell Receptors.Immunological reviews · 2025Review
- Sidedness matters: single-cell perspectives on left- and right-sided colorectal cancer.Frontiers in cell and developmental biology · 2025Review
- The constant domain of CRTAM is essential for high-affinity interaction with Nectin-like 2.Biochemistry and biophysics reports · 2024Article
- CD112 is an epithelial-to-mesenchymal transition-related and immunological biomarker in pan-cancer.Translational cancer research · 2024Article
- The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy.Frontiers in immunology · 2024Review
- Differences in Co-Expression of T Cell Co-Inhibitory and Co-Stimulatory Molecules with PD-1 Across Different Human Cancers.Journal of oncology research and therapy · 2024Article
- The nexus of natural killer cells and melanoma tumor microenvironment: crosstalk, chemotherapeutic potential, and innovative NK cell-based therapeutic strategies.Cancer cell international · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin-like adhesion molecules and thus plays a critical role in the innate immune response to malignant transformation. Although the TIGIT nectin-like protein-5 (necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor that is broadly over-expressed in breast and ovarian cancer, remains unknown. Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is most distal from the membrane with an affinity of 6 μm, which was moderately lower than the affinity observed for the TIGIT/necl-5 interaction (3.2 μm). The TIGIT/nectin-2 binding disrupted pre-assembled nectin-2 oligomers, suggesting that receptor-ligand and ligand-ligand associations are mutually exclusive events. Indeed, the crystal structure of TIGIT bound to the first immunoglobulin domain of nectin-2 indicated that the receptor and ligand dock using the same molecular surface and a conserved "lock and key" binding motifs previously observed to mediate nectin/nectin homotypic interactions as well as TIGIT/necl-5 recognition. Using a mutagenesis approach, we dissected the energetic basis for the TIGIT/nectin-2 interaction and revealed that an "aromatic key" of nectin-2 is critical for this interaction, whereas variations in the lock were tolerated. Moreover, we found that the C-C' loop of the ligand dictates the TIGIT binding hierarchy. Altogether, these findings broaden our understanding of nectin/nectin receptor interactions and have implications for better understanding the molecular basis for autoimmune disease and cancer.
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