Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Low affinity TCRs support regulatory T cell function in autoimmunity

ABSTRACT: Low affinity TCRs support regulatory T cell function in autoimmunity

PROVIDER: PRJNA416932 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6249600_1.fastq.gz	Fastqsanger.gz
	SRR6249600_2.fastq.gz	Fastqsanger.gz
	SRR6249610_1.fastq.gz	Fastqsanger.gz
	SRR6249610_2.fastq.gz	Fastqsanger.gz
	SRR6249620_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 96

Similar Datasets

Low affinity TCRs support regulatory T cell function in autoimmunity

Project description:Low affinity Tregs are important for controlling autoimmune diabetes.

2017-12-29 | GSE106467 | GEO

Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.

Project description:Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles. The results of this study suggest mechanistically distinct and potentially nonredundant roles for high- and low-affinity Tregs in controlling autoimmunity.

| S-EPMC5962277 | biostudies-literature

TCR affinity-dependent functional inhibition via PD-1 and SHP-1 phosphatase

Project description:To investigate gene expression changes associated with stimulation of TCRs of different affinity, primary CD8 T cells were transduced with sequence optimized TCRs of various affinities and stimulated for 6h. Gene expression was measured at baseline (0h) and after 6h after stimulation with low dose NY-ESO-1 multimer

2013-02-11 | E-GEOD-42922 | biostudies-arrayexpress

TCR affinity-dependent functional inhibition via PD-1 and SHP-1 phosphatase

2013-02-11 | GSE42922 | GEO

Low affinity CTCF binding drives transcriptional regulation whereas high affinity binding encompasses architectural functions.

Project description:Low affinity CTCF binding drives transcriptional regulation whereas high affinity binding encompasses architectural functions.

| PRJNA856492 | ENA

Eomes broadens the scope of CD8 T cell memory by inhibiting apoptosis in low-affinity cells

Project description:The memory CD8 T cell pool must select for high-affinity clones to efficiently counter re-infection yet must retain a level of clonal diversity to allow recognition of pathogens with mutated immuno-dominant epitopes. How this is mediated is unclear, especially in the context of a selective drive for antigen-affinity. We find that low-affinity memory exclusively depends on the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the pro-survival protein Bcl-2. At higher signal intensity T-bet is induced which suppresses Bcl-2, generating a survival advantage for low-affinity cells. High-affinity cells form memory independent of Eomes and have a proliferative advantage over low-affinity cells, which compensates for their survival deficit. Thus, we demonstrate on a molecular level how sufficient diversity of the memory pool is established in an environment of affinity-based selection.

2020-08-01 | GSE118174 | GEO

Transcriptional profiling of OT-1 cells during in vitro memory formation after high- or low-affinity priming

Project description:To understand the impact of TCR affinity during priming on memory formation, we performed transcriptional profiling of OT-1 cells at different time points after stimulation with high- or low-affinity ligands. Our findings indicate that low-affinity stimulaation is associated with earlier memory formation.

2020-01-06 | GSE102189 | GEO

ATLAS-seq: a novel microfluidic single-cell TCR screen for highly reactive antigen-specific TCRs

Project description:Clonotype selection of T cell receptors (TCRs) have been the core component of TCR therapy development. However, the conventional and widely used major histocompatibility complex (MHC) multimer staining technologies focus on high-affinity interactions between TCR and MHC-antigen complex, which may fail to identify TCRs with high efficacy for activating T cells. Here, we developed the Aptamer-based T Lymphocyte Activity Screening and sequencing (ATLAS-seq) method on a microfluidic platform. ATLAS-seq isolates and characterizes activated T cells using an aptamer-based fluorescent molecular sensor to monitor cytokine secretion from single-T cells upon antigen stimulation, followed by single-cell sequencing. As a proof of principle study, we used ATLAS-seq to screen cytomegalovirus (CMV)-reactive TCRs and identified a distinct clonotype population with a higher T cell activation level compared to one recovered by Dextramer staining method. Furthermore, we observed that ATLAS-seq selected TCR clonotypes are more efficient in target cell killing than those from Dextramer staining. Therefore, our ATLAS-seq can provide an efficient workflow to screen highly reactive antigen-specific TCR clonotypes for cancer immunotherapy.

2024-10-11 | GSE234359 | GEO

PRAME and CTCFL-reactive TCRs for the treatment of ovarian cancer

Project description:Recurrent disease emerges in the majority of patients with ovarian cancer (OVCA). Adoptive T-cell therapies with T-cell receptors (TCRs) targeting tumor-associated antigens (TAAs) are considered promising solutions for less-immunogenic ‘cold’ ovarian tumors. In order to treat a broader patient population, more TCRs targeting peptides derived from different TAAs binding in various HLA class I molecules are essential. By performing a differential gene expression analysis using mRNA-seq datasets, PRAME, CTCFL and CLDN6 were selected as strictly tumor-specific TAAs, with high expression in ovarian cancer and at least 20-fold lower expression in all healthy tissues of risk. In primary OVCA patient samples and cell lines we confirmed expression and identified naturally expressed TAA-derived peptides in the HLA class I ligandome. Subsequently, high-avidity T-cell clones recognizing these peptides were isolated from the allo-HLA T-cell repertoire of healthy individuals. Three PRAME TCRs and one CTCFL TCR of the most promising T-cell clones were sequenced, and transferred to CD8+ T cells. The PRAME TCR-T cells demonstrated potent and specific antitumor reactivity in vitro and in vivo. The CTCFL TCR-T cells efficiently recognized primary patient-derived OVCA cells, and OVCA cell lines treated with demethylating agent 5-aza-2′-deoxycytidine (DAC). The identified PRAME and CTCFL TCRs are promising candidates for the treatment of patients with ovarian cancer, and are an essential addition to the currently used HLA-A*02:01 restricted PRAME TCRs. Our selection of differentially expressed genes, naturally expressed TAA peptides and potent TCRs can improve and broaden the use of T-cell therapies for patients with ovarian cancer or other PRAME or CTCFL expressing cancers.

2023-03-10 | PXD040651 | Pride

Glycolysis Promotes Phosphoinositide 3-Kinase Signaling In Support of T Helper 17 Cell-Mediated Autoimmunity

Project description:Glycolysis Promotes Phosphoinositide 3-Kinase Signaling In Support of T Helper 17 Cell-Mediated Autoimmunity

| PRJNA692622 | ENA