Similar Datasets
Project description:Defects in T cell receptor (TCR) repertoire are proposed to predispose to autoimmunity. Here we show, by analyzing >2×108 TCRB sequences of circulating naive, central memory, reg- ulatory and stem cell-like memory CD4+ T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s (CDR3), in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. High frequency of short CDR3s is also observed in unproductive TCRB sequences, which are not subjected to thymic culling, suggesting that the shorter CDR3s arise independently of positive/negative selection. Moreover, TCRB CDR3 clonotypes expressed by autoantigen-specific CD4+ T cells are shorter compared with anti-viral T cells, and with those from healthy donors. Thus, early events in thymic T cell development and repertoire generation are abnormal in type 1 diabetes, which suggest that short CDR3s increase the potential for self-recognition, conferring heightened risk of autoimmune disease.
2024-07-22 | GSE272431 | GEO
Project description:To examine the microbiota abundance difference, we performed fecal 16s sequencing of wild type, TCRb-/-, TCRb-/- co-housed with WT and TCRb-/- receiving WT T cells.
2024-05-06 | GSE220867 | GEO
Project description:Thymic regulatory T cells (tTreg) are critical in maintenance of normal T cell immunity and tolerance. The role of TCR in tTreg cell selection remains incompletely understood. Here we assessed TCRa and TCRb sequences of tTreg and conventional thymic CD4+ T (Tconv) cells by high throughput sequencing. We identified ab TCR sequences that were unique to either tTreg or Tconv cells and found that these were distinct as recognized by machine learning (ML) algorithm and by preferentially used amino acid trimers in ab CDR3 of tTreg cells. In addition, a proportion of ab TCR sequences expressed by tTreg were also found in Tconv cells, and ML classified the great majority of these shared ab TCR sequences as characteristic of Tconv and not tTreg cells. These findings identify two populations of tTreg, one in which Treg fate is associated with unique properties of the TCR, and another with TCR properties characteristic of Tconv cells for which tTreg fate is determined by factors beyond TCR sequence.
2020-01-10 | GSE143291 | GEO
Project description:We report the application of single-molecule-based sequencing technology for mapping the Egr2 transcriptional program in developing thymic NKT. We found that Egr2 controls the induction of genes required for NKT development. Examination of developing NKT cells and thymocytes receiving a strong TCR signal in vivo by injecting 500ug anti-TCRb antibody.
2012-02-06 | E-GEOD-34254 | biostudies-arrayexpress
Project description:Tcrb locus V(D)J recombination is regulated by positioning at the nuclear periphery. Here we used DamID to profile Tcrb locus interactions with the nuclear lamina at high-resolution. We identified a lamina-associated domain (LAD) border composed of several CTCF binding elements that segregates active non-LAD from inactive LAD regions of the locus. Deletion of the LAD border caused an enhancer-dependent spread of H3K27ac from the active recombination center into recombination center-proximal LAD chromatin. This was associated with a disruption to LAD organization, increased chromatin looping to the recombination center, and increased transcription and recombination of recombination center-proximal gene segments. Our results show that a Tcrb locus LAD and LAD border are critical components of Tcrb locus gene regulation and suggest that LAD borders may generally function to constrain the activity of nearby enhancers.
2018-10-22 | GSE115582 | GEO
Project description:We co-cultured T cells with Mo-DCs exposed to ConA for 24 h and used multiplex PCR and next-generation sequencing to detect the TCRα repertoire.The length of the amino acids of CDR3 in each group was 4–59 amino acids, and all presented a normal distribution. Moreover, the length of the amino acids of CDR3 was not different between ConA and control groups. The number of clonotypes and unique clonotypes in the ConA group was increased significantly compared with that in control groups. However, the difference of high-frequency CDR3 amino-acid clonotypes between ConA and control groups was not significant (cutoff = 0.2%). Our results for the V and J gene segments of TCR diversity showed a marked increase in the number of clonotypes in the ConA group. The Shannon–Wiener Diversity Index of ConA was lower than that in the control group, and the top-20 V and J gene segments of ConA showed a higher usage frequency than that in the control group, but the difference between ConA and the control group was not significant. Collectively, these data indicated that ConA could reduce CDR3 diversity and augment usage of high-frequency CDR3.
2022-05-15 | GSE163933 | GEO
Project description:To analyze the TCR clonal repertoire, sorted CD44+CD8+T cells from brain and draining lyph nodes of T-aFGL2 treated tumor free mice were processed TCRa or TCRb RNA sequencing
2022-12-12 | GSE218756 | GEO
Project description:The study aims to identify intratumoral TCRb CD3R diversity, number and overlap between tumors from mice carrying bilateral CT26 tumors with a treatment group being injected in one tumor (Tumor_R) with a sustained release technology providing sustained release of R848 and RepSox (CarboCell TLR:TGFb, termed CC) and not injected in the contralateral tumor (Tumor_L) compared to untreated control mice (termed UT). The Mice bearing bilateral CT26 tumors received three unilateral (Tumor_R) CarboCell TLR:TGFb injections. Tumors were harvested one week after CarboCell treatment (31 days after inoculation). Untreated tumors were harvested 17 days after inoculation. Genomic DNA was extracted and purified from tumors using the DNeasy Blood & Tissue Kit (QIAGEN) according to the manufacturer's instructions. RNA-free genomic DNA was obtained by adding 4 μl RNase A (100 mg/ml, QIAGEN). Immunosequencing of TCRβ CDR3 regions was performed using the survey ImmunoSeq Assay (Adaptive Biotechnologies, Seattle, WA). Analysis were performed to identify the shared nucleotide sequences between the treated and untreated tumors. The sample overlap was also analysed to determine the extent to which rearrangements are shared between samples using the sample overlap tool to generate a Morisita Index. The tool will compute the specified overlap measure between injected and uninfected tumor on CarboCell TLR:TGFb mice and controls.
2024-07-15 | E-MTAB-14247 | biostudies-arrayexpress
Project description:We used an immature mouse T cell line engineered to express a biotinylated form of the cleaved form of Notch1 (ICN1). ICN1-bound sites were precipitated with streptavidin-coated beads and subjected to ChIP-sequencing. Beko cells correspond to a spontaneous T lymphoma immature cell line derived from a TCRb deficient mouse. These cells were engineered to express a biotin-tagged-ICN1 and the bacterial biotin ligase BirA (Bio-ICN1) or just BirA as a control (Bio). Chromatin from both cell lines was subjected to strepatavidin-mediated precipitation and subjected to sequencing with the Illumina GAII sequencer as single end 36 base pair reads.
2014-04-02 | E-GEOD-46114 | biostudies-arrayexpress
Project description:We report that in developing B cells individual enhancers of Igk make up super-enhancer cluster where contacts between its components rely on all constituents. Reduction of interaction frequency in enhancer knock-out cells is associated with deminished transcriptional output of enhancers and Igk locus. Moreover, we find that Igk enhancer MiEk has an effect on levels of CBFb enrichment on Tcrb enhancer, Eb afffecting Tcrb recombination and T cell development.
2016-05-26 | GSE80271 | GEO