Ontology highlight
ABSTRACT:
PROVIDER: PRJNA400603 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Using murine models that exclude variation in host genetics, environmental factors and tumour mutation burden, limiting variation between animals to naturally diverse TCRβ repertoires, we applied bulk TCRseq to study TCRβ repertoire dynamics in ICT responders and non-responders
2024-05-08 | GSE222575 | GEO
Project description:The T-cell receptor (TCR) is a highly polymorphic surface receptor that allows T-cells to recognize antigenic peptides presented on the major histocompatibility complex (MHC). Changes in the TCR repertoire have been observed in several autoimmune conditions, and these changes are suggested to predispose autoimmunity . Multiple lines of evidence have implied an important role for T-cells in the pathogenesis of Systemic Sclerosis (SSc), a complex autoimmune disease. One of the major questions regarding the roles of T-cells is whether expansion and activation of T-cells observed in the diseases pathogenesis is (auto)antigen driven. To investigate the temporal TCR repertoire dynamics in SSc, we performed high-throughput sequencing of CD4+ and CD8+ TCRβ chains on longitudinal samples obtained from four SSc patients collected over a minimum of two years. Repertoire overlap analysis revealed that samples taken from the same individual over time shared a high number of TCRβ sequences, indicating a clear temporal persistence of the TCRβ repertoire in CD4+ as well as CD8+ T-cells. Moreover, the TCRβs that were found with a high frequency at one time point were also found with a high frequency at the other time points (even after almost four years), showing that frequencies of dominant TCRβs are largely consistent over time. We also show that TCRβ generation probability and observed TCR frequency are not related in SSc samples, showing that clonal expansion and persistence of TCRβs is caused by antigenic selection rather than convergent recombination. Moreover, we demonstrate that TCRβ diversity is lower in CD4+ and CD8+ T-cells from SSc patients compared to healthy memory T-cells, as SSc TCRβ repertoires are largely dominated by clonally expanded persistent TCRβ sequences. Lastly, using “Grouping of Lymphocyte Interactions by Paratope Hotspots” (GLIPH2), we identify clusters of TCRβ sequences with homologous sequences that potentially recognize the same antigens and contain TCRβs that are persist in SSc patients. In conclusion, our results show that that CD4+ and CD8+ T-cells are highly persistent in SSc patients over time, and this persistence is likely a result from antigenic selection. Moreover, persistent TCRs form high similarity clusters with other (non-)persistent sequences, that potentially recognize the same epitopes. These data provide evidence for an (auto-)antigen driven expansion of CD4/CD8+ T-cells in Ssc.
2021-01-27 | GSE156980 | GEO
Project description:To assess TCR diversity in AC484-treated tumors we profiled the TCRβ chain repertoire from untreated, anti-PD-1-treated, or AC484-treated B16 tumours
2023-07-14 | GSE237374 | GEO
Project description:To investigate the influence of CNS3, a cis-regulatory element in the Foxp3 locus, on the selection of T cell antigen receptor (TCR) repertoire of regulator CD4+ T cells (Treg), we crossed Foxp3ΔCNS3-gfp or control Foxp3gfp mice to DO11.10 TCRβ transgene and Tcra-/+ background. We isolated Treg and conventional CD4+T cells from thymus, spleen and lymph nodes of Foxp3ΔCNS3-gfp DO11.10 TCRβ Tcra-/+ or Foxp3gfp DO11.10 TCRβ Tcra-/+ male littermates, and sequenced the TCRα chains. Analysis of the diversity of Complementary Determining Region 3 (CDR3) of TCRα showed a distinct clustering of CNS3-deficient Treg cells from the CNS3-sufficient ones.
2015-10-05 | GSE71162 | GEO
Project description:We report the application of TCRβ sequencing to understand T cell repertoire of matched blood and tumor samples pre and post treatment in EG7.OVA tumor bearing mice with OT-1 cell transfer. TCRβ sequencing demonstrated that OT-1 (CASSRANYEQYF) was the most abundant T-cell clone in both blood and tumors of mRBC‑OVA-4-1BBL-IL-12 treated mice. To investigate the effects of mRBC‑OVA-4-1BBL-IL-12 on immune memory, the T cell repertoire was also analyzed before and after EG7.OVA and EL4 tumor rechallenge in cured and treatment-naive mice. TCRβ sequencing on T cells in peripheral blood showed that OT-1 clones increased in frequency after EG7.OVA challenge in previously cured mice. OT-1 frequency did not increase in treatment-naïve mice after tumor challenge, indicating that the tumor alone is insufficient to drive OT-1 cell expansion. We also evaluated the frequencies of unique TCRβ sequences in T cell clones that significantly expanded post EL4 challenge (EL4 responsive TCR). Increased frequency of EL4-responsive TCRs upon each tumor challenge (EG7.OVA and EL4) was associated with complete responders (mice that rejected EL4 challenge), suggesting that T-cell-mediated protection against parental tumor antigens was generated prior to EL4 challenge. Partial responders (delayed tumor growth compared with naïve mice) had increases in EL4-responsive TCR frequencies after EL4 challenge but not during the EG7.OVA rechallenge, whereas the non-responder (tumor growth similar to naïve mice) had minimal increases in TCR frequencies upon EL4 challenge. Overall, the ability to control EL4 tumors correlated with the expansion of EL4-responsive TCR clones.
2021-03-13 | GSE168826 | GEO
Project description:T-cells can influence the post-myocardial infarction healing process. The fundamental role of T cells in adaptive immunity relies mainly on a diverse repertoire of T cell receptor (TCR) α and β chains that display unique antigen specificities. Thus, we performed high-throughput sequencing of the TCRβ chains on CD4+ T cells purified by fluorescence-activated cell sorting (FACS) from the heart and med-LNs of MI and sham-operated mice as an unbiased approach to screen for MI-related TCR signatures.
2019-08-14 | GSE117076 | GEO
Project description:The T cell receptor (TCR) determines the specificity and affinity for both foreign and self-peptides presented by MHC. It is established that self-pMHC reactivity impacts T cell function, but it has been challenging to identify TCR sequence features that predict T cell fate. To discern patterns distinguishing TCRs from naïve CD4+ T cells with low versus high self-pMHC reactivity, we used data from 42 mice to train a machine learning (ML) algorithm that predicts self-reactivity directly from TCRβ sequences. This approach revealed that n-nucleotide additions and acidic amino acids weaken selfreactivity. We tested our ML predictions of TCRβ sequence self-reactivity using retrogenic mice. Extrapolating our analyses to independent datasets, we found high predicted self-reactivity for regulatory CD4+ T cells and low predicted self-reactivity for T cells responding to chronic infection. Our analyses suggest a potential trade-off between repertoire diversity and self-reactivity intrinsic to the architecture of a TCR repertoire.
2023-01-09 | GSE221703 | GEO
Project description:Here we report bulk TCR sequencing data associated with open repertoire murine CD4+, CD4+CD8+, and CD8+ T cells isolated from B16 melanoma tumor resections
2022-05-20 | GSE203187 | GEO