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Anti-CD4 treatment affects TCR repertoire of CD8+ T cells

ABSTRACT: Anti-CD4 treatment affects TCR repertoire of CD8+ T cells

PROVIDER: PRJNA751392 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15319983_1.fastq.gz	Fastqsanger.gz
	SRR15319983_2.fastq.gz	Fastqsanger.gz
	SRR15319984_1.fastq.gz	Fastqsanger.gz
	SRR15319984_2.fastq.gz	Fastqsanger.gz
	SRR15319985_1.fastq.gz	Fastqsanger.gz

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Anti-CD4 treatment affects TCR repertoire of CD8+ T cells

Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, elicits robust anti-tumor immunity in various cancers by increasing tumor-infiltrating lymphocytes and promoting CD8+ T cell reactivity against tumor cell-derived antigens. We conducted TCR repertoire analysis of anti-CD4-exposed endogenous CD8+ T cells to investigate the expansion pattern of the cell population.

2021-08-03 | GSE181280 | GEO

TCR repertoire analysis revealed the mobilization of novel CD8+ T cell clones into Cancer-Immunity Cycle following anti-CD4 antibody administration

Project description:Depletion of CD4+ cells by anti-CD4 monoclonal antibody (anti-CD4 mAb) induces expansion of tumor-reactive CD8+ T cells and exhibits strong antitumor effects in several murine tumor models. However, whether the anti-CD4 mAb treatment activates particular or a broad variety of tumor-reactive CD8+ T cell clones is not answered. To investigate the changes of TCR repertoire induced by the anti-CD4 mAb treatment, we performed unbiased high throughput TCR sequencing in a B16F10 mouse subcutaneous melanoma model.

2019-02-07 | GSE115425 | GEO

Gene expression of TCR-alpha/beta CD4- CD8- human T cells

Project description:The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity. TCR-alpha-beta+ CD25- T cells from healthy human individuals were sorted into CD4+, CD8+, and CD4-CD8- T cells. Cell lysis and RNA extraction was performed immediately. RNA from each cell subset was pooled.

2009-05-16 | E-GEOD-16130 | biostudies-arrayexpress

TCR repertoire analysis revealed the highly conserved TCR repertoire in the bilateral tumor in mice

Project description:Temporal analysis of T-cell receptor (TCR) repertoire has been used to monitor treatment-induced changes in antigen-specific T cells in patients with cancer. However, lack of experimental model that allows the temporal analysis of TCR repertoire in same individual in homogeneous population limit the understanding of causal relationship between changes in TCR repertoire and antitumor responses. A bilateral tumor model, in which tumor cells were inoculated into the bilateral backs of mice, can be used for temporal analysis in TCR repertoire. In this study, we examined the prerequisite for this strategy: TCR repertoire are conserved between the bilateral tumor with same growth rate. The bilateral tumors with equivalent tumor size and draining lymph nodes (dLN) were collected 13 days after the tumor inoculation to analyze the TCR repertoire of CD4+ and CD8+ T cells. Most of the tumor-infiltrating T-cell clones were highly conserved between the bilateral tumors, and the extent of clonal expansion was equivalent. In addition, the similarity between bilateral tumors were equivalent to the heterogeneity in one side of the tumor. The similarity of TCR repertoire in the bilateral dLN was markedly lower than that of the tumor, suggesting that tumor-reactive T-cell clones induced independently in each dLN were integrated during recirculation and then infiltrated the tumor. These findings suggest that our bilateral tumor model is suitable for temporal monitoring of TCR repertoire to evaluate temporal and treatment-induced changes in tumor-reactive T-cell clones.

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Deep exploration of the TCR CDR3β repertoire specific for viral CD4 T cell epitopes inside the circulating T cell repertoire

Project description:This study provides an in-depth analysis of the diversity of the CD4 TCR CDR3β repertoire specific to Influenza A (HA) and Epstein-Barr virus (EBNA) epitopes. Epitope-specific CD4 T cells from 13 healthy donors were enriched using a short-term culture step, isolated based on activation markers, and sequenced for their TCR CDR3β region using high-throughput sequencing. The frequency of each clonotype were then identified within the complete circulating CD4 T-cell CDR3β repertoire. For both epitopes, the clonotype distribution was markedly skewed, with a small number of highly expanded clones comprising approximately 60% of the repertoire, alongside numerous low-frequency clonotypes. VJ gene usage and motif preferences differed between the two peptides, highlighting epitope-specific TCR selectivity. The response was predominantly composed of private T-cell clonotypes. The proportion of public clonotypes can increase among donors sharing HLA class II molecules and reveals in HLA-unrelated donors the level of TCR promiscuity. Overall, our data demonstrate that CD4 T-cell responses to these viral epitopes are polyclonal and highly personalized. The modest overlap of clonotypes between donors, coupled with a long tail of low-frequency clones, suggests that the full diversity of the epitope-specific T-cell repertoire is likely broader than previously estimated.

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Transcription profiling of mouse CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies

Project description:Comparison of gene expression changes in CD4+CD8+ thymocytes following engagement of TCR with anti-Valpha or Vbeta antibodies

2007-09-28 | E-GEOD-1448 | biostudies-arrayexpress

Single cell RNAseq coupled with TCR repertoire analysis of thymocytes in thymus autonomy and turnover

Project description:Wild type thymi were transplanted into wild recipients (turnover) or Rag2-/-gc-/- mice (autonomy) and, after 28 days of transplant, thymocytes (double negative 3 and 4, immature CD8 single positive and CD4 CD8 double positive) were sorted and single cell RNAseq and TCR repertoire analysis performed

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Mtb HLA-E tetramer sorted CD8+ T-cells have a diverse TCR repertoire

Project description:HLA-E molecules can present self and pathogen-derived peptides to both NK-cells and T-cells. T-cells that recognize HLA-E peptides via their T-cell receptor (TCR) are termed donor-unrestricted T-cells due to restricted allelic variation of HLA-E. The composition and repertoire of HLA-E TCRs is not known so far. We performed TCR sequencing on CD8+ T-cells from 21 individuals recognizing HLA-E tetramers (TM) folded with 2 Mtb HLA-E restricted peptides. We sorted HLA-E Mtb TM+ and TMCD8+ T-cells directly ex vivo and performed bulk RNA-sequencing and single cell TCR sequencing. The identified TCR repertoire was diverse and showed no conservation between and within individuals. TCRs selected from our single cell TCR sequencing data could be activated upon HLA-E/peptide stimulation, although not robust, reflecting potentially weak interactions between HLA-E peptide complexes and TCRs. Thus, HLA-E Mtb specific T-cells have a highly diverse TCR repertoire.

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TCR Repertoire of CD4+ T cells in Human Lymph Nodes

Project description:TCR Repertoire of CD4+ T cells in Human Lymph Nodes

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TCR Repertoire of CD4+ T cells in Human Lymph Nodes

Project description:TCR Repertoire of CD4+ T cells in Human Lymph Nodes

| PRJNA434344 | ENA