ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Ca2+ release from the endoplasmic reticulum of NY-ESO-1-specific T cells is modulated by the affinity of TCR and by the use of the CD8 coreceptor.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Microfluidic T Cell Selection by Cellular Avidity.Advanced healthcare materials · 2022Article
- CD5 Deficiency Alters Helper T Cell Metabolic Function and Shifts the Systemic Metabolome.Biomedicines · 2022Article
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
- Signal strength controls the rate of polarization within CTLs during killing.The Journal of cell biology · 2021Article
- Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Relationship of 2D Affinity to T Cell Functional Outcomes.International journal of molecular sciences · 2020Review
- Article
- Regulation of T Helper Cell Fate by TCR Signal Strength.Frontiers in immunology · 2020Review
- NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses.Frontiers in immunology · 2019Article
- T cell cytolytic capacity is independent of initial stimulation strength.Nature immunology · 2018Article
- Physiological function of phospholipase D2 in anti-tumor immunity: regulation of CD8Scientific reports · 2018Article
- CalQuoScientific reports · 2017Article
- Evaluating frequency and quality of pathogen-specific T cells.Nature communications · 2016Article
- Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells.Science translational medicine · 2016Article
- Calcium Dynamics of Ex Vivo Long-Term Cultured CD8+ T Cells Are Regulated by Changes in Redox Metabolism.PloS one · 2016Article
- T Cells and Gene Regulation: The Switching On and Turning Up of Genes after T Cell Receptor Stimulation in CD8 T Cells.Frontiers in immunology · 2016Review
- The functional contribution of calcium ion flux heterogeneity in T cells.Immunology and cell biology · 2015Review
- Preferential Coupling of the NAADP Pathway to Exocytosis in T-Cells.Messenger (Los Angeles, Calif. : Print) · 2015Article
- T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells.Clinical and experimental immunology · 2015Article
- Scrutinizing calcium flux oscillations in T lymphocytes to deduce the strength of stimulus.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Although several cancer immunotherapy strategies are based on the use of analog peptides and on the modulation of the TCR affinity of adoptively transferred T cells, it remains unclear whether tumor-specific T cell activation by strong and weak TCR stimuli evoke different Ca(2+) signatures from the Ca(2+) intracellular stores and whether the amplitude of Ca(2+) release from the endoplasmic reticulum (ER) can be further modulated by coreceptor binding to peptide/MHC. In this study, we combined functional, structural, and kinetic measurements to correlate the intensity of Ca(2+) signals triggered by the stimulation of the 1G4 T cell clone specific to the tumor epitope NY-ESO-1(157-165). Two analogs of the NY-ESO-1(157-165) peptide, having similar affinity to HLA-A2 molecules, but a 6-fold difference in binding affinity for the 1G4 TCR, resulted in different Ca(2+) signals and T cell activation. 1G4 stimulation by the stronger stimulus emptied the ER of stored Ca(2+), even in the absence of CD8 binding, resulting in sustained Ca(2+) influx. In contrast, the weaker stimulus induced only partial emptying of stored Ca(2+), resulting in significantly diminished and oscillatory Ca(2+) signals, which were enhanced by CD8 binding. Our data define the range of TCR/peptide MHC affinities required to induce depletion of Ca(2+) from intracellular stores and provide insights into the ability of T cells to tailor the use of the CD8 coreceptor to enhance Ca(2+) release from the ER. This, in turn, modulates Ca(2+) influx from the extracellular environment, ultimately controlling 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.