ArticleNature communications2020
Structural characterization of the ICOS/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies.
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 36 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Global research prospects and trends in TFH cells and tumors: a bibliometric analysis.Frontiers in oncology · 2025Pooled it
- Potent neutralization of Rift Valley fever virus mediated by monoclonal antibodies via concurrent inhibition of attachment and fusion.Emerging microbes & infections · 2026Article
- An inducible co-stimulator ligand (ICOSL)-based peptide therapy for proteinuric kidney diseases targeting αvβ3 integrin.Molecular biomedicine · 2026Article
- Molecular Architecture and Clinical Landscape of Immune Checkpoint Receptors and Ligands.Antibodies (Basel, Switzerland) · 2026Review
- An ICOSL-armed oncolytic adenovirus activates CD4BMC medicine · 2026Article
- Chemical Synthesis of Homogeneous Glycoproteins for the Elucidation of Glycan Functions.Advances in experimental medicine and biology · 2026Review
- The emerging role of B cells in immune-mediated demyelinating diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- ICOSL: more than a trigger of ICOS function.Cell communication and signaling : CCS · 2025Review
- CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting.Bioorganic & medicinal chemistry letters · 2025Review
- Unraveling cooperative and competitive interactions within protein triplets in the human interactome.Scientific reports · 2025Article
- Primary Cutaneous CD4+ Small/Medium-Sized T-Cell Lymphoproliferative Disorder: A Retrospective Cohort Study of 40 Adult Patients.The American Journal of dermatopathology · 2025Article
- Directed evolution and modular integration of a high-affinity ICOS-L variant for potent T cell-mediated tumor elimination.Journal of biological engineering · 2025Article
- Ig or Not Ig? That Is the Question: The Nucleating Supersecondary Structure of the Ig-Fold and the Extended Ig Universe.Methods in molecular biology (Clifton, N.J.) · 2025Article
- From Virtual Screens to Cellular Target Engagement: New Small Molecule Ligands for the Immune Checkpoint LAG-3.ACS medicinal chemistry letters · 2024Article
- Triscysteine disulfide-directing motifs enabling design and discovery of multicyclic peptide binders.Nature communications · 2024Article
- Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer.International journal of molecular sciences · 2024Article
- Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles.iScience · 2024Article
- Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.Immunity · 2024Article
- The Role of the CD28 Family Receptors in T-Cell Immunomodulation.International journal of molecular sciences · 2024Review
- The Expression and Prognostic Significance of ICOS in NSCLC Integrated Pan-Cancer and Multi-Omics Analyses.International journal of medical sciences · 2024Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The inducible co-stimulator (ICOS) is a member of the CD28/B7 superfamily, and delivers a positive co-stimulatory signal to activated T cells upon binding to its ligand (ICOS-L). Dysregulation of this pathway has been implicated in autoimmune diseases and cancer, and is currently under clinical investigation as an immune checkpoint blockade. Here, we describe the molecular interactions of the ICOS/ICOS-L immune complex at 3.3 Å resolution. A central FDPPPF motif and residues within the CC' loop of ICOS are responsible for the specificity of the interaction with ICOS-L, with a distinct receptor binding orientation in comparison to other family members. Furthermore, our structure and binding data reveal that the ICOS N110 N-linked glycan participates in ICOS-L binding. In addition, we report crystal structures of ICOS and ICOS-L in complex with monoclonal antibodies under clinical evaluation in immunotherapy. Strikingly, antibody paratopes closely mimic receptor-ligand binding core interactions, in addition to contacting peripheral residues to confer high binding affinities. Our results uncover key molecular interactions of an immune complex central to human adaptive immunity and have direct implications for the ongoing development of therapeutic interventions targeting immune checkpoint receptors.
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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.