ArticleScience signaling2018
Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 89 citations in OpenAlex.
- High-Precision Intrinsic Interactome Elucidation of Chimeric Antigen Receptors via Photocatalytic Micromapping (μMap-CAR).Journal of the American Chemical Society · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Systematic optimization of PD-L1 and CLDN18.2 CAR-T designs identifies a bicistronic dual-target, double-CD3ζ architecture with enhanced antitumor activity in gastric cancer.Frontiers in immunology · 2026Article
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- T cells in cancer: mechanistic insights and therapeutic advances.Biomarker research · 2025Review
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells.Nature biomedical engineering · 2025Article
- Early events in TCR signaling - the evolving role of ITAMs.Frontiers in immunology · 2025Review
- Advances in CAR optimization strategies based on CD28.Frontiers in immunology · 2025Review
- Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti-tumour activity.Cell proliferation · 2024Article
- Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma.Experimental hematology & oncology · 2024Review
- Novel immunotherapeutics against LGR5 to target multiple cancer types.EMBO molecular medicine · 2024Article
- Chimeric antigen receptor T cells in the treatment of osteosarcoma (Review).International journal of oncology · 2024Review
- Endogenous Signaling Molecule Activating (ESMA) CARs: A Novel CAR Design Showing a Favorable Risk to Potency Ratio for the Treatment of Triple Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Controlling the Potency of T Cell Activation Using an Optically Tunable Chimeric Antigen Receptor.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells.Immunotherapy advances · 2024Article
- CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides.Nature immunology · 2023Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The T cell antigen receptor (TCR) recognizes peptides from pathogenic proteins bound in the major histocompatibility complex (MHC). To convert this binding event into downstream signaling, the TCR complex contains immunoreceptor tyrosine-based activation motifs (ITAMs) that act as docking sites for the cytoplasmic tyrosine kinase ZAP-70. Unique among antigen receptors, the TCR complex uses 10 ITAMs to transduce peptide-MHC binding to the cell interior. Using synthetic, drug-inducible receptor-ligand pairs, it was found that greater ITAM multiplicity primarily enhanced the efficiency with which ligand binding was converted into an intracellular signal. This manifested as an increase in the fraction of cells that became activated in response to antigen, and a more synchronous initiation of TCR-proximal signaling, rather than direct amplification of the intracellular signals. Exploiting these findings, the potency and selectivity of chimeric antigen receptors targeted against cancer were substantially enhanced by modulating the number of encoded ITAMs.
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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.