ArticleNature immunology2012
Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.
Article in Nature immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 236 citations in OpenAlex.
- Engineering cytokines for cancer immunotherapy: a systematic review.Frontiers in immunology · 2023Pooled it
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Computational modeling and expression of recombinant interleukin 15-R-Tf-D-LP4 peptide fusion protein: a potent candidate for hepatocellular carcinoma.Biotechnology letters · 2026Article
- In Vitro Inhibition of STAT5 Signaling Limits CD8+ T-cell Exhaustion and Improves Outcomes in Adoptive T-cell Therapy.Cancer immunology research · 2026Article
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- Computational identification and experimental validation of shared diagnostic biomarkers and gene signatures across HLA-B27-associated immune-mediated diseases.Journal of translational medicine · 2026Article
- Article
- Total Chemical Synthesis of Interleukin-15 and Interleukin-2: Taming Protein Hydrophobicity and Aggregation by a Versatile Solubilizing Strategy.Angewandte Chemie (International ed. in English) · 2026Article
- PEG-RLI: A Long-Acting IL-15 Agonist That Produces Massive Levels of CD8Pharmaceutics · 2026Article
- VISTA drives pancreatic tumor progression through modulation of the tumor-associated macrophage polarity.Nature communications · 2026Article
- Integrating T cell signaling and metabolism to enhance T cell engager responses in solid tumors.Frontiers in immunology · 2026Review
- IL-15 Promotes Inflammatory Th17 Cells in the Intestine.Inflammatory bowel diseases · 2025Article
- Exploring genomic signatures of selection for adaptation and resilience in nomadic Belahi cattle in the tropical climate.Molecular biology reports · 2025Article
- Structure and function of therapeutic antibodies approved by the US FDA in 2024.Antibody therapeutics · 2025Review
- Adjusting the scope of natural killer cells in cancer therapy.Cellular & molecular immunology · 2025Review
- Concurrent intratumoural TNature biomedical engineering · 2025Article
- Rapid assay development for low input targeted proteomics using a versatile linear ion trap.Nature communications · 2025Article
- Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccine.NPJ vaccines · 2025Article
- Neoleukin-2/15-armored CAR-NK cells sustain superior therapeutic efficacy in solid tumors via c-Myc/NRF1 activation.Signal transduction and targeted therapy · 2025Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rβ and the common γ-chain (γ(c)). Here we found that in the structure of the IL-15-IL-15Rα-IL-2Rβ-γ(c) quaternary complex, IL-15 binds to IL-2Rβ and γ(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Rα-IL-2Rβ-γ(c) complex, despite their different receptor-binding chemistries. IL-15Rα substantially increased the affinity of IL-15 for IL-2Rβ, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rβ-γ(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Rα versus IL-15Rα determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.
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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.