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Predicting Antigen-Specificities of Orphan T Cell Receptors from Cancer Patients with TCRpcDist

ABSTRACT: Predicting Antigen-Specificities of Orphan T Cell Receptors from Cancer Patients with TCRpcDist

PROVIDER: PRJNA1050266 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27153694.fastq.gz	Fastqsanger.gz
	SRR27153695.fastq.gz	Fastqsanger.gz
	SRR27153696.fastq.gz	Fastqsanger.gz
	SRR27153697.fastq.gz	Fastqsanger.gz
	SRR27153698.fastq.gz	Fastqsanger.gz

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Predicting Antigen-Specificities of Orphan T Cell Receptors from Cancer Patients with TCRpcDist

Project description:Approaches to analyze and cluster T-cell receptor (TCR) repertoires to reflect antigen specificity are critical for the diagnosis and prognosis of immune-related diseases and the development of personalized therapies. Sequence-based approaches showed success but remain restrictive, especially when the amount of experimental data used for the training is scarce. Structure-based approaches which represent powerful alternatives, notably to optimize TCRs affinity toward specific epitopes, show limitations for large-scale predictions. To handle these challenges, TCRpcDist is presented, a 3D-based approach that calculates similarities between TCRs using a metric related to the physico-chemical properties of the loop residues predicted to interact with the epitope. By exploiting private and public datasets and comparing TCRpcDist with competing approaches, it is demonstrated that TCRpcDist can accurately identify groups of TCRs that are likely to bind the same epitopes. Importantly, the ability of TCRpcDist is experimentally validated to determine antigen specificities (neoantigens and tumor-associated antigens) of orphan tumor-infiltrating lymphocytes (TILs) in cancer patients. TCRpcDist is thus a promising approach to support TCR repertoire analysis and TCR deorphanization for individualized treatments including cancer immunotherapies.

2024-08-22 | GSE249741 | GEO

High-throughput determination of the antigen specificities of T cell receptors in single cells

Project description:High-throughput determination of the antigen specificities of T cell receptors in single cells

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High-throughput determination of the antigen specificities of T cell receptors in single cells

Project description:High-throughput determination of the antigen specificities of T cell receptors in single cells

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NR2C/F orphan receptors induce telomere-genome rearrangements in ALT

Project description:Most sarcomas have complex karyotype and are characterized by multiple chromosomal rearrangements. Moreover, sarcomas very frequently maintain their telomeres by recombination in the process called Alternative Lengthening of Telomeres (ALT) which enables their continuous growth and immortalization. Previously our group showed that orphan receptors bind specifically to the ALT telomeres and that their presence is important for the ALT mechanism. In these studies we focus on the function of orphan receptors at the telomeres and their contribution to telomeric recombination. We demonstrate that orphan receptors induce proximity of their binding sites in telomeric and genomic context and reveal novel aspects of ALT which are telomere-genome rearrangements which can underlie complexity of sarcomas. Our data perturb the dogma of telomere function in protecting the genome integrity. Here we show that in some cases telomeres may in fact drive genomic instability and chromosomal rearrangements by recombination with genomic sites. Characterization of TRF2 and orphan receptor NR2F/C2 binding sites in ALT (-) and ALT (+) cells.

2015-02-23 | E-GEOD-46237 | biostudies-arrayexpress

NR2C/F orphan receptors induce telomere-genome rearrangements in ALT

2015-02-23 | GSE46237 | GEO

Elucidation of roles of Nr4a nuclear orphan receptors and Foxp3 in thymic Treg cell development

Project description:Both Nr4a family nuclear orphan receptors and Foxp3 had been revealed to be crucial transcription factors in Treg cell development. In this study, to reveal their roles in a Treg cell developmental transcriptional programs, we compared transcriptomes among wild-type conventional CD4 T (Tconv) cells, wild-type Treg cells, Nr4a-triple-knockout (Nr4a-TKO) Treg precursor (preTreg) cells, and Foxp3-KO preTreg cells by microarray.

2017-02-10 | GSE94727 | GEO

Transcriptional profiling of monocytes deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 reveals distinct signalling roles related to antigen presentation and viral response.

Project description:Transcriptional profiling of monocytes deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 reveals distinct signalling roles related to antigen presentation and viral response.

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Epigenomic profiling of enhancers identifies orphan nuclear receptors NR2F1 and NR2F2 as novel regulators of human neural crest.

Project description:Combining an in vitro hNCC differentiation protocol with epigenomic profiling, we provide the first whole-genome characterization of cis-regulatory elements in this highly relevant cell type. With this data at hand, we have characterized the chromatin state and dynamics of all human gene promoters during the course of NCC in vitro differentiation. Most importantly, we have identified a large cohort of active and NCC-specific enhancers, which we showed to be functionally relevant in vivo, in the context of embryonic development. Finally, through sequence analysis of the identified NCC enhancers, we uncovered the orphan nuclear receptors NR2F1 and NR2F2 as novel hNCC transcriptional regulators both in vitro and in vivo. Genome-wide analysis of H3K27ac in chicken neural crest cells (NCC) obtained from stage 11-14 or stage 20 embryos

2012-09-13 | E-GEOD-38066 | biostudies-arrayexpress

Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion

Project description:Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion

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NR4A1 and NR4A2 orphan nuclear receptors regulate endothelial to hematopoietic transition in mouse hematopoietic stem cell specification

Project description:Hematopoietic stem cells (HSCs) sustain life-long hematopoiesis and emerge during mid-gestation from hemogenic endothelial (HE) progenitors via an endothelial to hematopoietic transition (EHT). The full scope of molecular mechanisms governing this process remains unclear. The NR4A subfamily of orphan nuclear receptors act as tumour suppressors in myeloid leukemogenesis and have never been implicated in HSC specification. Here, we report that Nr4a1 and Nr4a2 expression is upregulated in hemogenic endothelium during EHT. Progressive genetic ablation of Nr4a gene dosage results in a gradual decrease in numbers of nascent c-Kit+ hematopoietic progenitors in developing embryos, c-Kit+ cell cluster size in the dorsal aorta, and a block in HSC maturation, revealed by an accumulation of pro-HSCs and pre-HSC-type I cells and decreased numbers of pre-HSC-type II cells. Consistent with these observations, cells isolated from E11.5 Nr4a1-/-; Nr4a2-/- aorta-gonads-mesonephros (AGM) are devoid of in vivo long-term hematopoietic repopulating potential. Molecularly, employing spatial transcriptomic analysis we determined that the genetic ablation of Nr4a1 and Nr4a2 prevents NOTCH signaling from being downregulated in intra-aortic clusters and thus for pro-HSCs to mature into HSCs. Interestingly, this defect is partially rescued via ex vivo culture of dissected AGMs with SCF, IL3 and FLT3L, which may bypass NOTCH-dependent regulation. Overall, our data reveal a novel role for the NR4A family of orphan nuclear receptors in EHT.

2024-11-04 | GSE281058 | GEO

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