Engagement of TCR with antibodies
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE1448 | GEO | 2005/01/01
SECONDARY ACCESSION(S): PRJNA89999
REPOSITORIES: GEO
Similar Datasets
Project description:Comparison of gene expression changes in CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies
2007-09-28 | E-GEOD-1448 | biostudies-arrayexpress
Project description:T-cells are a critical component of the adaptive immune system and play a key role in immunological surveillance. Upon engagement of T-cell receptor (TCR), CD4+ and CD8+ T-cells acquire effector functions through a complex interplay between mRNA and proteins yet to be fully understood. In this study we explored the temporal transcriptomic and proteomic changes mediated by TCR engagement in both CD4+ and CD8+ T-cells. T-cells isolated from peripheral blood mononuclear cells of three healthy volunteers over 90% purity as assessed by fluorescence-labeled flow cytometry (FACS) and monoclonal antibodies were in vitro activated using anti-CD3/CD28 Dynabeads. Samples obtained before the activation, and 6h, 12h, 24h, 3 days (d), and 7d following activation were analyzed using label-free data-dependent acquisition mass spectrometry-based proteomics (DDA-proteomics), to identify the temporal dynamics in CD4+ and CD8+ T-cell proteomes during activation. A parallel analysis was performed to explore the transcriptomic dynamics during T-cell activation. Our data revealed a time-dependent dissociation between the T-cell transcriptome and proteome: the onset of activation was driven by rapid changes of the mRNA content with sluggish increase in protein synthesis, ultimately leading to rewired transcriptome and proteome. We surprisingly found that CD4+ and CD8+ T-cells became transcriptionally more divergent while their proteome became more similar over the time course of activation. Several changes in the content of mRNAs and proteins associated with metabolic pathways were detected through KEGG pathway analysis, revealing a transient disconnection between the aerobic glycolysis and glutaminolysis pathways in activated T-cells. This dataset provides a comprehensive framework for understanding the main temporal changes that regulate metabolic pathways governing the acquisition of effector functions by CD4+ and CD8+ T-cells.
2023-12-28 | PXD038810 | Pride
Project description:To define the physiological properties of TCR signaling, We investigated the global dynamic view of TCR-dependent phosphorylation with the use of thymocytes stimulated with antibodies to CD3 to mimic TCR activation
2022-02-22 | PXD000969 | Pride
Project description:A single cell TCR-RNAseq data set comprised of CD4+CD8+ and CD4+ thymocytes and CD25+ Treg progenitors (TRP), Foxp3lo TRP, de novo developing Tregs and recirculating mature Tregs.
2022-05-31 | GSE195820 | GEO
Project description:Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis translates TCR signal strength into proportional activation of enhancers and genes essential for T cell function. CD4+ T cells from transgenic AND mice were sequenced under the conditions indicated. Replicates are included for each type of data (RNA-Seq, ChIP-Seq), and are numbered accordingly. The No Peptide condition serves as the untreated control for the peptide-treated samples, and inputs are provided for ChIP-Sequencing samples.
2016-06-01 | E-GEOD-69545 | biostudies-arrayexpress
Project description:Title of Publication: Histone Deacetylase 7 Regulates Cell Survival and TCR Signaling in CD4/CD8 Double-Positive Thymocytes Abstract of publicaton: CD4/CD8 double-positive (DP) thymocytes express the transcriptional repressor Histone Deacetylase 7 (HDAC7), a class IIa HDAC that is exported from the cell nucleus after T cell receptor (TCR) engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in thymocytes, and regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR J segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAP kinase activity that contributes to the observed loss of viability. Remarkably, the activity of Protein Kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining auto-excitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions. Goal of Microarray experiment: We did these experiments to determine how alteration of the function of HDAC7, a site-specific and signal-dependent repressor of transcription, changes gene expression in CD4/CD8 DP thymocytes. Three biological replicate samples were prepared for each non-wild type mouse strain (Samples 7-18). Six biological replicates were prepared for the wild type strain (Samples 1-6). Total RNA was prepared from isolated CD4/CD8 Double-positive thymocytes and labeled with the Affymetrix Whole-Transcript labeling protocol. Labeled probes were hybridized to one Affymetrix Mouse Gene 1.0ST array each. Data from .cel files were normalized using RMA, in normalization groups representing each of the binary comparisons made. These binary comparisons between sample groups represent gene expression changes due to loss of HDAC7 (samples 1-3 vs. 7-9), transgenic expression of an HDAC7-VP16 fusion protein (samples 4-6 vs. 10-12), positive thymic selection (samples 1-6 vs. samples 11-15), and negative thymic selection (Samples 11-15 vs. samples 16-18).
2011-04-06 | E-GEOD-26488 | biostudies-arrayexpress
Project description:The biological functions of histone demethylases Jmjd3 and Utx remain poorly understood. We assessed such functions in developing T cells, using conditional (CD4-Cre-mediated) gene disruption, by inactivating Kdm6a and Kdm6b, respectively encoding Utx and Jmjd3, in immature CD4+CD8+ thymocytes. We compared microarray gene expression in mature (Va2hi CD24lo) mutant and wild-type CD4+CD8- thymocytes carrying the OT-II TCR transgene. We show that Jmjd3 and Utx redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Mature (Va2hi CD24lo) CD4 thymocytes were sorted from freshly prepared single-cell suspensions OT-II TCR transgenic thymocytes deficient for Utx and Jmjd3 (dKO, CD4-Cre conditional deletion of floxed Kdm6a and Kdm6b alleles), and from Cre-negative controls (wild-type). Total RNA was extracted from sorted thymocytes using the RNeasy Plus Mini Kit (Qiagen) and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturer’s recommendation. Data is generated from 3 replicates from each experiment.
2015-09-17 | E-GEOD-70363 | biostudies-arrayexpress
Project description:Durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a source for the pool of effector T cells, and in the absence of their cognate antigen, they are able to preserve their quantity through a process of self-renewal. However, it remains unknown how TCR engagement impacts the self-renewal capacity of Tpex in settings of continued antigen exposure. Here, we used a Lewis lung carcinoma model that elicits an optimal or attenuated TCR signal in CD8 T cells to investigate its effect on Tpex persistence during tumor development. Longitudinal phenotyping and single-cell transcriptomics of tumor-specific T cells revealed that formation of the Tpex reservoir in tumor-draining lymph nodes, and its subsequent replenishment of intratumoral Tpex, is dependent on optimal TCR engagement. Notably, adoptive transfer of optimally primed Tpex into a tumor setting with attenuated TCR stimulation significantly accelerates their terminal differentiation, contrasting to the sustained self-renewal occuring with optimal TCR stimulation. This TCR-reinforced Tpex development and self-renewal is coupled to proximal positioning to dendritic cell niches and epigenetic imprinting that involves increased chromatin accessibility at Egr2 and Tcf1 target loci. Collectively, our study highlights the critical role of TCR engagement in sustaining Tpex during tumor progression
2024-04-05 | GSE262816 | GEO
Project description:Durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a source for the pool of effector T cells, and in the absence of their cognate antigen, they are able to preserve their quantity through a process of self-renewal. However, it remains unknown how TCR engagement impacts the self-renewal capacity of Tpex in settings of continued antigen exposure. Here, we used a Lewis lung carcinoma model that elicits an optimal or attenuated TCR signal in CD8 T cells to investigate its effect on Tpex persistence during tumor development. Longitudinal phenotyping and single-cell transcriptomics of tumor-specific T cells revealed that formation of the Tpex reservoir in tumor-draining lymph nodes, and its subsequent replenishment of intratumoral Tpex, is dependent on optimal TCR engagement. Notably, adoptive transfer of optimally primed Tpex into a tumor setting with attenuated TCR stimulation significantly accelerates their terminal differentiation, contrasting to the sustained self-renewal occuring with optimal TCR stimulation. This TCR-reinforced Tpex development and self-renewal is coupled to proximal positioning to dendritic cell niches and epigenetic imprinting that involves increased chromatin accessibility at Egr2 and Tcf1 target loci. Collectively, our study highlights the critical role of TCR engagement in sustaining Tpex during tumor progression
2024-04-05 | GSE262843 | GEO
Project description:Durability of an antitumor immune response is mediated in part by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a source for the pool of effector T cells, and in the absence of their cognate antigen, they are able to preserve their quantity through a process of self-renewal. However, it remains unknown how TCR engagement impacts the self-renewal capacity of Tpex in settings of continued antigen exposure. Here, we used a Lewis lung carcinoma model that elicits an optimal or attenuated TCR signal in CD8 T cells to investigate its effect on Tpex persistence during tumor development. Longitudinal phenotyping and single-cell transcriptomics of tumor-specific T cells revealed that formation of the Tpex reservoir in tumor-draining lymph nodes, and its subsequent replenishment of intratumoral Tpex, is dependent on optimal TCR engagement. Notably, adoptive transfer of optimally primed Tpex into a tumor setting with attenuated TCR stimulation significantly accelerates their terminal differentiation, contrasting to the sustained self-renewal occuring with optimal TCR stimulation. This TCR-reinforced Tpex development and self-renewal is coupled to proximal positioning to dendritic cell niches and epigenetic imprinting that involves increased chromatin accessibility at Egr2 and Tcf1 target loci. Collectively, our study highlights the critical role of TCR engagement in sustaining Tpex during tumor progression
2024-04-05 | GSE262842 | GEO