ArticleNature communications2015
TCR ITAM multiplicity is required for the generation of follicular helper T-cells.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Weak SLP-76/PLC-γ1 interaction fine-tunes T cell receptor signal strength to optimize T cell responsiveness.Nature communications · 2026Article
- 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
- Weak SLP-76-PLC-γ1 interaction in the LAT-nucleated multi-protein complex fine-tunes TCR signal strength to optimize T cell responsiveness.bioRxiv : the preprint server for biology · 2025Article
- Deciphering the deterministic role of TCR signaling in T cell fate determination.Frontiers in immunology · 2025Review
- Early events in TCR signaling - the evolving role of ITAMs.Frontiers in immunology · 2025Review
- TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation.The Journal of experimental medicine · 2024Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides.Nature immunology · 2023Article
- Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- The role of endocytic trafficking in antigen T cell receptor activation.Biomedical journal · 2022Review
- Antigen-Specific CD4Frontiers in immunology · 2022Article
- Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells.Frontiers in immunology · 2022Article
- Article
- Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire.PLoS pathogens · 2021Article
- A TCR mechanotransduction signaling loop induces negative selection in the thymus.Nature immunology · 2018Article
- DUSP6 mediates T cell receptor-engaged glycolysis and restrains TProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Regulatory mechanisms in T cell receptor signalling.Nature reviews. Immunology · 2018Review
- TCR signal strength controls the differentiation of CD4Science immunology · 2018Article
- Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density.Science signaling · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We generated 'knock-in' mice that express non-signalling CD3ζ chains in lieu of wild-type CD3ζ. Here we demonstrate that ITAM multiplicity is important for the development of innate-like T-cells and follicular helper T-cells, events that are known to require strong/sustained TCR-ligand interactions, but is not essential for 'general' T-cell responses including proliferation and cytokine production or for the generation of a diverse antigen-reactive TCR repertoire.
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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.