Transcription profiling of mouse CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Nicholas Robert John Gascoigne
PROVIDER: E-GEOD-1448 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Thymocyte stimulation by anti-TCR-beta, but not by anti-TCR-alpha, leads to induction of developmental transcription program.
Niederberger Nathalie N Buehler Lukas K LK Ampudia Jeanette J Gascoigne Nicholas R J NR
Journal of leukocyte biology 20050120 5
Anti-T cell receptor (aTCR) antibody (Ab) stimulation of T cells results in TCR down-modulation and T cell activation. Differences in the effect of anti-alpha-chain and beta-chain Ab have been reported on thymocytes. Anti-beta-chain Ab but not anti-alpha-chain reagents cause long-term TCR down-modulation. However, both types of Ab result in TCR cross-linking and activate early steps in signal transduction. In this study, we show that TCR internalization and calcium flux, hallmarks of T cell acti ...[more]
Similar Datasets
Project description:Comparison of gene expression changes in CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies Keywords: parallel sample
2005-01-01 | GSE1448 | 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 | 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
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 | GSE262844 | GEO
Project description:We performed ChIP-Seq for hallmark TFs (Ets1, Runx1), histone modification marks (H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3), total RNA Pol II, short RNA-Seq as well as nucleosome mapping mainly in murine Rag2 -/- thymocytes. We also performed ChIP-Seq for E47 as well as nucleosome mapping, gene expression microarray analysis in CD4+ CD8+ WT and Ets1-/- DP thymocytes. Overall, we find a key role for the transcription factor Ets1, contributing towards alpha beta T cell lineage commitment via differential transactivation of stage-specific genes orchestrated by dynamic, co-association -mediated chromatin remodeling, as well as transcription dependent generation of a specialized chromatin structure at the TCR beta locus. Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes Gene expression analysis of Ets1-/- CD4+ CD8+ thymocytes
2015-12-19 | E-GEOD-73849 | biostudies-arrayexpress
Project description:We performed ChIP-Seq for hallmark TFs (Ets1, Runx1), histone modification marks (H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3), total RNA Pol II, short RNA-Seq as well as nucleosome mapping mainly in murine Rag2 -/- thymocytes. We also performed ChIP-Seq for E47 as well as nucleosome mapping, gene expression microarray analysis in CD4+ CD8+ DP thymocytes. Overall, we find a key role for the transcription factor Ets1, contributing towards alpha beta T cell lineage commitment via differential transactivation of stage-specific genes orchestrated by dynamic, co-association -mediated chromatin remodeling, as well as transcription dependent generation of a specialized chromatin structure at the TCR beta locus. Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes This Series represents gene expression microarray data.
2014-04-01 | E-GEOD-56357 | biostudies-arrayexpress
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:Screening for mouse cDNA that was highly expressed in positive-selector H-2b AND-TCR-transgenic thymocytes using Affymetrix Murine Genome arrays. Experiment Overall Design: 2 thymocytes, H-2b AND-TCR-transgenic thymocytes and C57BL/6 thymocytes, were analyzed by duplicate hybridization.
2007-12-07 | E-GEOD-3909 | biostudies-arrayexpress
Project description:We performed ChIP-Seq for hallmark TFs (Ets1, Runx1), histone modification marks (H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3), total RNA Pol II, short RNA-Seq as well as nucleosome mapping mainly in murine Rag2 -/- thymocytes. We also performed ChIP-Seq for E47 as well as nucleosome mapping, gene expression microarray analysis in CD4+ CD8+ DP thymocytes. Overall, we find a key role for the transcription factor Ets1, contributing towards alpha beta T cell lineage commitment via differential transactivation of stage-specific genes orchestrated by dynamic, co-association -mediated chromatin remodeling, as well as transcription dependent generation of a specialized chromatin structure at the TCR beta locus. Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes
2014-04-01 | GSE56357 | GEO