ArticleNature communications2020
IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Functional immune profiling translates T cell dynamics into predictive biomarkers for myeloma immunotherapy.Leukemia · 2026Article
- DNA-directed assembly of multivalent lipid nanoparticles for targeted T cell gene delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- The effects of insulin-regulated aminopeptidase inhibition with HA08 on recognition memory acquisition and spatial working memory under reversed circadian conditions in male rats.IBRO neuroscience reports · 2025Article
- Article
- Pseudouridine reprogramming in the human T-cell epitranscriptome: from primary to immortalized states.RNA (New York, N.Y.) · 2025Article
- CARD11 signaling regulates CD8Nature immunology · 2025Article
- Integrin linked kinase and threonine tyrosine kinase modulate TCR signaling.Scientific reports · 2025Article
- IRAP Drives Ribosomal Degradation to Refuel Energy for Platelet Activation during Septic Thrombosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Discovery of New Nanomolar Selective IRAP Inhibitors.Journal of medicinal chemistry · 2025Article
- Inhibition of IRAP Enhances the Expression of Pro-Cognitive Markers Drebrin and MAP2 in Rat Primary Neuronal Cells.International journal of molecular sciences · 2024Article
- The Discovery of New Inhibitors of Insulin-Regulated Aminopeptidase by a High-Throughput Screening of 400,000 Drug-like Compounds.International journal of molecular sciences · 2024Article
- Sex- and time-dependent role of insulin regulated aminopeptidase in lipopolysaccharide-induced inflammation.Frontiers in immunology · 2024Article
- Inhibition of insulin-regulated aminopeptidase confers neuroprotection in a conscious model of ischemic stroke.Scientific reports · 2023Article
- Article
- Endocytosis in cancer and cancer therapy.Nature reviews. Cancer · 2023Review
- Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Optical sensing and control of T cell signaling pathways.Frontiers in physiology · 2023Review
- Hydrogen Peroxide Induced Toxicity Is Reversed by the Macrocyclic IRAP-Inhibitor HA08 in Primary Hippocampal Cell Cultures.Current issues in molecular biology · 2022Article
- The role of endocytic trafficking in antigen T cell receptor activation.Biomedical journal · 2022Review
- The emerging multifunctional roles of ERAP1, ERAP2 and IRAP between antigen processing and renin-angiotensin system modulation.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell receptor (TCR) activation is modulated by mechanisms such as TCR endocytosis, which is thought to terminate TCR signalling. Here we show that, upon internalization, TCR continues to signal from a set of specialized endosomes that are crucial for T cell functions. Mechanistically, TCR ligation leads to clathrin-mediated internalization of the TCR-CD3ζ complex, while maintaining CD3ζ signalling, in endosomal vesicles that contain the insulin responsive aminopeptidase (IRAP) and the SNARE protein Syntaxin 6. Destabilization of this compartment through IRAP deletion enhances plasma membrane expression of the TCR-CD3ζ complex, yet compromises overall CD3ζ signalling; moreover, the integrity of this compartment is also crucial for T cell activation and survival after suboptimal TCR activation, as mice engineered with a T cell-specific deletion of IRAP fail to develop efficient polyclonal anti-tumour responses. Our results thus reveal a previously unappreciated function of IRAP-dependent endosomal TCR signalling in T cell activation.
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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.