ArticleNature immunology2013
Distinct TCR signaling pathways drive proliferation and cytokine production in T cells.
Article in Nature immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 221 citations in OpenAlex.
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- Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions.Oncology reviews · 2026Article
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- Targeting the roots of myeloid malignancies with T cell receptors.Nature reviews. Cancer · 2025Review
- Combined Adaptive Immune Mechanisms Mediate Cardiac Injury After COVID-19 Vaccination.Circulation · 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
- Membrane receptors cluster phosphatidylserine to activate LC3-associated phagocytosis.Nature cell biology · 2025Article
- Comprehensive Analysis of TCR and BCR Repertoires: Insights into Methodologies, Challenges, and Applications.Genomics & informatics · 2025Review
- ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs.Nature communications · 2025Article
- Early events in TCR signaling - the evolving role of ITAMs.Frontiers in immunology · 2025Review
- The CD8Immunity · 2024Article
- ER-associated degradation adapter Sel1L is required for CD8Cell reports · 2024Article
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- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics.Science immunology · 2024Article
- TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation.The Journal of experimental medicine · 2024Article
- TIM-3, LAG-3, or 2B4 gene disruptions increase the anti-tumor response of engineered T cells.Frontiers in immunology · 2024Article
- A self-activated and protective module enhances the preclinical performance of allogeneic anti-CD70 CAR-T cells.Frontiers in immunology · 2024Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The physiological basis and mechanistic requirements for a large number of functional immunoreceptor tyrosine-based activation motifs (ITAMs; high ITAM multiplicity) in the complex of the T cell antigen receptor (TCR) and the invariant signaling protein CD3 remain obscure. Here we found that whereas a low multiplicity of TCR-CD3 ITAMs was sufficient to engage canonical TCR-induced signaling events that led to cytokine secretion, a high multiplicity of TCR-CD3 ITAMs was required for TCR-driven proliferation. This was dependent on the formation of compact immunological synapses, interaction of the adaptor Vav1 with phosphorylated CD3 ITAMs to mediate the recruitment and activation of the oncogenic transcription factor Notch1 and, ultimately, proliferation induced by the cell-cycle regulator c-Myc. Analogous mechanistic events were also needed to drive proliferation in response to weak peptide agonists. Thus, the TCR-driven pathways that initiate cytokine secretion and proliferation are separable and are coordinated by the multiplicity of phosphorylated ITAMs in TCR-CD3.
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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.