ArticleThe Journal of experimental medicine1999
T cell receptor (TCR) antagonism without a negative signal: evidence from T cell hybridomas expressing two independent TCRs.
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 28 papers.
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Who cites it
28 citing papers in PubMed, 71 citations in OpenAlex.
- Vaccination Targeting Native Receptors to Enhance the Function and Proliferation of Chimeric Antigen Receptor (CAR)-Modified T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- 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
- Targeting of tumor cells by custom antigen transfer: a novel approach for immunotherapy of cancer.Frontiers in oncology · 2023Article
- Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding.International journal of molecular sciences · 2021Article
- Novel Nested Peptide Epitopes Recognized by CD4Vaccines · 2020Article
- Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor.Nature communications · 2014Article
- 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
- A CD1d-dependent antagonist inhibits the activation of invariant NKT cells and prevents development of allergen-induced airway hyperreactivity.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Loss of T cell-mediated antitumor immunity after construct-specific downregulation of retrovirally encoded T-cell receptor expression in vivo.Cancer gene therapy · 2009Article
- The T cell receptor's alpha-chain connecting peptide motif promotes close approximation of the CD8 coreceptor allowing efficient signal initiation.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor.Immunity · 2008Article
- A role for CD8 in the developmental tuning of antigen recognition and CD3 conformational change.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Ligand detection and discrimination by spatial relocalization: A kinase-phosphatase segregation model of TCR activation.Biophysical journal · 2006Article
- Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope.Molecular immunology · 2006Article
- Nonstimulatory peptides contribute to antigen-induced CD8-T cell receptor interaction at the immunological synapse.Nature immunology · 2005Article
- T cell receptor engagement by peptide-MHC ligands induces a conformational change in the CD3 complex of thymocytes.The Journal of experimental medicine · 2005Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antagonist peptides inhibit T cell responses by an unknown mechanism. By coexpressing two independent T cell receptors (TCRs) on a single T cell hybridoma, we addressed the question of whether antagonist ligands induce a dominant-negative signal that inhibits the function of a second, independent TCR. The two receptors, Valpha2Vbeta5 and Valpha2Vbeta10, restricted by H-2Kb and specific for the octameric peptides SIINFEKL and SSIEFARL, respectively, were coexpressed on the same cell. Agonist stimulation demonstrated that the two receptors behaved independently with regard to antigen-induced TCR downregulation and intracellular biochemical signaling. The exposure of one TCR (Valpha2Vbeta5) to antagonist peptides could not inhibit a second independent TCR (Valpha2Vbeta10) from responding to its antigen. Thus, our data clearly demonstrate that these antagonist ligands do not generate a dominant-negative signal which affects the responsiveness of the entire cell. In addition, a kinetic analysis showed that even 12 h after engagement with their cognate antigen and 10 h after reaching a steady-state of TCR internalization, T cells were fully inhibited by the addition of antagonist peptides. The window of susceptibility to antagonist ligands correlated exactly with the time required for the responding T cells to commit to interleukin 2 production. The data support a model where antagonist ligands can competitively inhibit antigenic peptides from productively engaging the TCR. This competitive inhibition is effective during the entire commitment period, where sustained TCR engagement is essential for full 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.