Single cell gene expression of ESAT-6 specific CD4 TCR Transgenic T-cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE265891 | GEO | 2025/02/24
REPOSITORIES: GEO
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Project description:Accurately assigning antigen specificity to T cell receptor (TCR) sequences is challenging due to the complexity of the TCR-antigen recognition process in humans. We developed the Peptide-Driven Identification of TCRs (PDI-TCR) assay, a novel method combining in vitro expansion with peptide pools, bulk TCR sequencing, and statistical analysis to identify antigen-specific TCRs from human blood. A key feature of PDI-TCR is its ability to account for bystander T cell expansion using both antigen-specific and non-specific peptide pools, distinguishing true antigen-specific TCRs from the unspecific ones. We applied PDI-TCR to Tuberculosis (TB) patients, sampling blood at diagnosis and throughout therapy, and Mycobacterium tuberculosis (Mtb)-sensitized healthy individuals (IGRA+). We identified hundreds of Mtb-specific and unspecific TCRs, and in combination with single-cell mRNA and TCR sequencing of CD4 T cells, we characterized the transcriptome of Mtb-specific and unspecific T cells in each cohort. Mtb-specific T cells were highly diverse, with the presence of short-lived effector phenotypes only in TB at diagnosis and memory phenotypes maintained through treatment. In contrast, unspecific T cells were more clonally restricted and expanded, cytotoxic, and maintained through treatment. Thus, PDI-TCR is a powerful tool for identifying antigen-specific TCRs. Combined with single-cell sequencing of T cell populations, it enables direct ex vivo monitoring of antigen-specific T cells.
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Project description:Screening for mouse cDNA that was highly expressed in positive-selector H-2b AND-TCR-transgenic thymocytes using Affymetrix Murine Genome arrays. Experiment Overall Design: 2 thymocytes, H-2b AND-TCR-transgenic thymocytes and C57BL/6 thymocytes, were analyzed by duplicate hybridization.
2007-12-07 | E-GEOD-3909 | biostudies-arrayexpress
Project description:Previous studies suggest that type I and type II CRISPR-Cas systems were employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium bovis (M. bovis) and Mycobacterium tuberculosis (M. tuberculosis) possess integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2~6, cas10, cas6) were significantly upregulated under oxidative stress treatment. To explore the function of type III-A CRSIRP-Cas system, Total CRISPR system (TCR) mutant strain was generated in M. bovis Bacille Calmette-Guérin (BCG). Deletion of TCR results in increased sensitivity in response to H2O2 and reduced cell envelope integrity. By using RNA-Seq, 590 differential expression genes were found in mutant for TCR, of which 220 genes were upregulated and 370 genes were downregulated, indicating an important role of TCR in controlling gene expression in mycobacteria. Consistently, disrupting TCR results in poor intracellular survival in vivo and in vitro. Moreover, we showed for the first time that TCR contributed to the regulation of regulatory T cell population, supporting a role of TCR in modulating host immunity. These observations demonstrate that type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, may be a potential target for therapy.
2021-02-05 | GSE166137 | GEO
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2014-08-29 | GSE57736 | GEO
Project description:Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected with M. tuberculosis monocytes from both, healthy elders (a tuberculosis susceptibility group) and elderly tuberculosis patients, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns of these genes regardless of whether they were obtained from younger or elder patients. Only one of the detected genes corresponded to a cytokine: IL-26, a member of the IL-10 cytokine family that we found downregulated in infected monocytes from tuberculosis patients. We have analyzed total RNA from Mycobacterium tuberculosis infected monocytes. We have isolated CD14+ cells (monocytes) from peripheral blood mononuclear cells by magnetic separation, and infected them for 4 days with 1 bacterium per monocyte. Blood donors were 7 elderly patients with pulmonary tuberculosis (average age: 83 years; sex: 3 men and 4 women) and 8 non-tuberculous volunteers (81 years, 6 men and 2 women).
2014-08-29 | E-GEOD-57736 | biostudies-arrayexpress
Project description:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis)
2015-12-08 | GSE70812 | GEO
Project description:We developed the Peptide-Driven Identification of TCRs (PDI-TCR), an approach that leverages antigen-specific peptide pools, bulk TCR sequencing, and statistical analyses to pinpoint antigen-specific TCRs. We discerned antigen-specific TCRs within a group of active tuberculosis (ATB) patients and individuals with a positive Interferon-γ release assay (IGRA+). We found Mtb-specific effectors to have an HLA-DR+ Th1* phenotype, and to be exclusive to active disease. Conversely, HLA-DR- Mtb-specific T cells appeared in Th1 cells in both ATB and IGRA+ cohorts. We also identified Cross-reactive T cells, that were abundant ex vivo regardless of disease state having a cytotoxic phenotype.
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Project description:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis) Two strains each with two conditions experiment, Rv (Mycobacterium tuberculosis wild type strain) high manganese vs. low manganese and ST70 (mntR mutant strain of Mycobacterium tuberculosis) high manganese vs. low manganese. Number of biological replicates is 3 for each condition for each strain.
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Project description:Jamshidi2007 - Genome-scale metabolic network
of Mycobacterium tuberculosis (iNJ661)
This model is described in the article:
Investigating the metabolic
capabilities of Mycobacterium tuberculosis H37Rv using the in
silico strain iNJ661 and proposing alternative drug
targets.
Jamshidi N, Palsson BØ.
BMC Syst Biol 2007; 1: 26
Abstract:
BACKGROUND: Mycobacterium tuberculosis continues to be a
major pathogen in the third world, killing almost 2 million
people a year by the most recent estimates. Even in
industrialized countries, the emergence of multi-drug resistant
(MDR) strains of tuberculosis hails the need to develop
additional medications for treatment. Many of the drugs used
for treatment of tuberculosis target metabolic enzymes.
Genome-scale models can be used for analysis, discovery, and as
hypothesis generating tools, which will hopefully assist the
rational drug development process. These models need to be able
to assimilate data from large datasets and analyze them.
RESULTS: We completed a bottom up reconstruction of the
metabolic network of Mycobacterium tuberculosis H37Rv. This
functional in silico bacterium, iNJ661, contains 661 genes and
939 reactions and can produce many of the complex compounds
characteristic to tuberculosis, such as mycolic acids and
mycocerosates. We grew this bacterium in silico on various
media, analyzed the model in the context of multiple
high-throughput data sets, and finally we analyzed the network
in an 'unbiased' manner by calculating the Hard Coupled
Reaction (HCR) sets, groups of reactions that are forced to
operate in unison due to mass conservation and connectivity
constraints. CONCLUSION: Although we observed growth rates
comparable to experimental observations (doubling times ranging
from about 12 to 24 hours) in different media, comparisons of
gene essentiality with experimental data were less encouraging
(generally about 55%). The reasons for the often conflicting
results were multi-fold, including gene expression variability
under different conditions and lack of complete biological
knowledge. Some of the inconsistencies between in vitro and in
silico or in vivo and in silico results highlight specific loci
that are worth further experimental investigations. Finally, by
considering the HCR sets in the context of known drug targets
for tuberculosis treatment we proposed new alternative, but
equivalent drug targets.
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2024-10-15 | BIOMD0000001095 | BioModels