ArticleNature communications2021
Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review.Current pharmaceutical design · 2024Pooled it
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Molecular Architecture and Clinical Landscape of Immune Checkpoint Receptors and Ligands.Antibodies (Basel, Switzerland) · 2026Review
- Ligand non-competitive GITR antibody prevents formation of the obligatory signal-triggering GITRL: GITR stoichiometry.Scientific reports · 2025Article
- GITR triggering has limited impact on HIV-specific CD8 T-cell function but enhances HIV transcription reactivation from latently infected CD4 T-cells.Scientific reports · 2025Article
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Exploring the role of APRIL in autoimmunity: implications for therapeutic targeting in systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome.Frontiers in immunology · 2025Review
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- Regulatory T cells in immune checkpoint blockade antitumor therapy.Molecular cancer · 2024Review
- Exploring the Role of GITR/GITRL Signaling: From Liver Disease to Hepatocellular Carcinoma.Cancers · 2024Review
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Memory regulatory T cells in pregnancy.Frontiers in immunology · 2023Review
- Activation Markers on B and T Cells and Immune Checkpoints in Autoimmune Rheumatic Diseases.International journal of molecular sciences · 2022Review
- Optimal target saturation of ligand-blocking anti-GITR antibody IBI37G5 dictates FcγR-independent GITR agonism and antitumor activity.Cell reports. Medicine · 2022Article
- Therapeutic antibody activation of the glucocorticoid-induced TNF receptor by a clustering mechanism.Science advances · 2022Article
- An acetonic extract and secondary metabolites from the endolichenic fungusFrontiers in pharmacology · 2022Article
- Structural delineation and phase-dependent activation of the costimulatory CD27:CD70 complex.The Journal of biological chemistry · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor-ligand interface and receptor-receptor interface; the unique C-terminal receptor-receptor enables higher order structures on the membrane. Human GITR-GITRL has potential to form a hexameric network of membrane complexes, while murine GITR-GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor-receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.