ArticleThe Journal of experimental medicine1999
Partially phosphorylated T cell receptor zeta molecules can inhibit T cell activation.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 111 citations in OpenAlex.
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- Early events in TCR signaling - the evolving role of ITAMs.Frontiers in immunology · 2025Review
- CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides.Nature immunology · 2023Article
- Kinetic proofreading through the multi-step activation of the ZAP70 kinase underlies early T cell ligand discrimination.Nature immunology · 2022Article
- Role of inhibitory signaling in peripheral B cell tolerance.Immunological reviews · 2022Review
- Lymphocytes and Trogocytosis-Mediated Signaling.Cells · 2021Review
- Computational Model of Chimeric Antigen Receptors Explains Site-Specific Phosphorylation Kinetics.Biophysical journal · 2018Article
- Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells.eLife · 2016Article
- Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling.Immunological reviews · 2015Review
- Phenotypic models of T cell activation.Nature reviews. Immunology · 2014Review
- A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function.Retrovirology · 2014Article
- CD3ζ-based chimeric antigen receptors mediate T cell activation via cis- and trans-signalling mechanisms: implications for optimization of receptor structure for adoptive cell therapy.Clinical and experimental immunology · 2014Article
- Termination of immune activation: an essential component of healthy host immune responses.Journal of innate immunity · 2014Review
- Phosphatase regulation of immunoreceptor signaling in T cells, B cells and mast cells.Current opinion in immunology · 2013Review
- Molecular insights for optimizing T cell receptor specificity against cancer.Frontiers in immunology · 2013Article
- Trogocytosis results in sustained intracellular signaling in CD4(+) T cells.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- How the TCR balances sensitivity and specificity for the recognition of self and pathogens.Nature immunology · 2012Review
- Article
- Opposite effects of endogenous peptide-MHC class I on T cell activity in the presence and absence of CD8.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- ITAM-mediated signaling by the T-cell antigen receptor.Cold Spring Harbor perspectives in biology · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The T cell receptor complex (TCR) zeta chain is constitutively tyrosine phosphorylated specifically at two of the six zeta immunoreceptor tyrosine-based activation motif (ITAM) tyrosine residues in resting peripheral T cells. Further phosphorylation of zeta is induced by both agonist and antagonist ligands of the TCR, with agonists inducing complete phosphorylation of the zeta ITAM tyrosines. After antagonist stimulation, zeta phosphorylation is incomplete and generates discrete forms of partially phosphorylated ITAMs. Here, we mutate specific tyrosines in chimeric human CD8-zeta molecules to reflect phosphorylation in resting T cells as well as phosphorylation induced by agonist and antagonist ligands. We demonstrate that such partially phosphorylated TCR-zeta species can inhibit IL-2 production in T cell hybridomas and proliferation in T cell clones. This reveals a previously unrecognized, inhibitory function of partially phosphorylated ITAMs. These findings support the concept that TCR antagonism can arise through the generation of an inhibitory signal within the TCR complex and that constitutive zeta phosphorylation in resting T cells is an inhibitory signaling environment.
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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.