ArticleThe Journal of experimental medicine1999
Cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement delivers an inhibitory signal through the membrane-proximal region in the absence of the tyrosine motif in the cytoplasmic tail.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 93 citations in OpenAlex.
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy.Cancer discovery · 2024Article
- Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies.Nature cancer · 2024Article
- Mechanistic Insights into the Inhibition of a Common CTLA-4 Gene Mutation in the Cytoplasmic Domain.Molecules (Basel, Switzerland) · 2024Article
- CTLA-4 antibody ipilimumab negatively affects CD4Cancer immunology, immunotherapy : CII · 2019Article
- Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens.Cancer cell · 2018Article
- Description of CD8Journal of immunology research · 2018Review
- Confusing signals: recent progress in CTLA-4 biology.Trends in immunology · 2015Review
- T cell activation is reduced by the catalytically inactive form of protein tyrosine phosphatase SHP-2.International journal of clinical and experimental medicine · 2015Article
- A screen for endocytic motifs.Traffic (Copenhagen, Denmark) · 2010Article
- SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels.Immunological reviews · 2009Review
- Checkpoint blockade in cancer immunotherapy.Advances in immunology · 2006Review
- Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by the costimulatory molecule CTLA-4.Molecular and cellular biology · 2005Article
- Surface cytotoxic T lymphocyte-associated antigen 4 partitions within lipid rafts and relocates to the immunological synapse under conditions of inhibition of T cell activation.The Journal of experimental medicine · 2002Article
- Activation and inhibition of lymphocytes by costimulation.The Journal of clinical investigation · 2002Review
- Anergy in peripheral memory CD4(+) T cells induced by low avidity engagement of T cell receptor.The Journal of experimental medicine · 2001Article
- CD28, CTLA-4 and their ligands: who does what and to whom?Immunology · 2000Review
- EMBO WORKSHOP REPORT: lymphocyte antigen receptor and coreceptor signaling Siena, Italy, November 6-10, 1999.The EMBO journal · 2000Article
- Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif ((165)YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain-containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling remains unclear. Here, we report a new mechanism of negative signaling based on the analysis of murine T cell clones transfected with various mutants of CTLA-4. Upon T cell activation by cross-linking with anti-CD3 and anti-CD28 antibodies, CTLA-4 engagement inhibited both proliferation and interleukin 2 production in tyrosine mutants as well as in wild-type CTLA-4 transfectants. Furthermore, the mutant CTLA-4 lacking most of the cytoplasmic region strongly suppressed interleukin 2 production as well. These data suggest that negative signals by CTLA-4 could be mediated through the membrane-proximal region of CTLA-4 but not through the YVKM motif and that the association of CTLA-4 with SHP-2 is not required for CTLA-4-mediated suppression of T cell activation.
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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.