ArticleThe Journal of clinical investigation2013
SHP-1 phosphatase activity counteracts increased T cell receptor affinity.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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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
82 citing papers in PubMed, 121 citations in OpenAlex.
- Protocol for a cohort study: evaluating the effect of neoadjuvant immunochemotherapy on intraoperative remifentanil consumption during IoC2-guided anesthesia in elderly patients with esophageal cancer.Annals of medicine · 2026Observational
- Beyond traditional roles: vitamin D and erythropoietin as immune modulators in kidney diseases.Clinical kidney journal · 2026Review
- Loss of SHP-1 in CD11cFrontiers in immunology · 2026Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.Frontiers in immunology · 2026Article
- A comparative mathematical modeling study of phenotypic approaches to T cell activation.Scientific reports · 2025Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.bioRxiv : the preprint server for biology · 2025Article
- Increase of Intracellular Zinc Levels Rather Than Zinc Influx Inhibits Interleukin-2 Production in Zinc Supplemented Jurkat Cells.Cell biochemistry and function · 2025Article
- Phage display enables machine learning discovery of cancer antigen-specific TCRs.Science advances · 2025Article
- Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition.Journal for immunotherapy of cancer · 2025Article
- Multi-omic analyses reveal PTPN6's impact on tumor immunity across various cancers.Scientific reports · 2025Article
- Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.Molecular cancer · 2024Review
- Preclinical model for evaluating human TCRs against chimeric syngeneic tumors.Journal for immunotherapy of cancer · 2024Article
- T-Switch: A specificity-based engineering platform for developing safe and effective T cell therapeutics.Immunity · 2024Article
- Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation.Cellular and molecular life sciences : CMLS · 2024Article
- Enhanced T cell receptor specificity through framework engineering.Frontiers in immunology · 2024Article
- PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior.Neuron · 2023Article
- Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors.Nature communications · 2023Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Electroacupuncture Alleviates CFA-Induced Inflammatory Pain via PD-L1/PD-1-SHP-1 Pathway.Molecular neurobiology · 2023Article
- Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors.The Journal of cell biology · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (K(d) < 1 μM) lead to drastic functional declines. Using human CD8(+) T cells engineered with TCRs of incremental affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity-associated loss of function. As compared with cells expressing TCR affinities generating optimal function (K(d) = 5 to 1 μM), those with supraphysiological affinity (K(d) = 1 μM to 15 nM) showed impaired gene expression, signaling, and surface expression of activatory/costimulatory receptors. Preferential expression of the inhibitory receptor programmed cell death-1 (PD-1) was limited to T cells with the highest TCR affinity, correlating with full functional recovery upon PD-1 ligand 1 (PD-L1) blockade. In contrast, upregulation of the Src homology 2 domain-containing phosphatase 1 (SHP-1/PTPN6) was broad, with gradually enhanced expression in CD8(+) T cells with increasing TCR affinities. Consequently, pharmacological inhibition of SHP-1 with sodium stibogluconate augmented the function of all engineered T cells, and this correlated with the TCR affinity-dependent levels of SHP-1. These data highlight an unexpected and global role of SHP-1 in regulating CD8(+) T cell activation and responsiveness and support the development of therapies inhibiting protein tyrosine phosphatases to enhance T cell-mediated immunity.
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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.