Expression data from NP366-374/Db and PA224-233/Db CD103 positive and negative T-cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE107448 | GEO | 2017/11/29
SECONDARY ACCESSION(S): PRJNA420093
REPOSITORIES: GEO
Similar Datasets
Project description:Expression data from NP366-374/Db and PA224-233/Db CD103 positive and negative T-cells
| PRJNA420093 | ENA
Project description:T lymphocytes leverage T-cell receptor (TCR) recognition of aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on altered cells to protect the mammalian host from infectious pathogens and cancerous transformations. While adaptive immunity requires efficient TCR performance, comparison metrics are widely limited to force-free assays. Recent data reveals, however, that mechanical load on the TCR-pMHC bond resulting from cellular motions between a T cell-antigen presenting cell conjugate formed during immune surveillance tunes TCR specificity and sensitivity. Here, we cloned TCRs from lung resident CD8 T cells following influenza A virus (IAV) infection directed against two immunodominant epitopes, the luminous nucleoprotein NP366-374 /Db and sparse acid polymerase PA224-233/Db pMHCs, arrayed at >1000 vs <10 copies/cell, respectively. Using optical tweezers-based methods to apply biologically relevant loads, we observe that certain TCRs belonging to the NP repertoire require many ligands for activation while others only few, functioning in analogue or digital modes, correspondingly. In contrast, prevalent TCRs tested in the PA repertoire all perform digitally. When held at a critical force, moreover, even digital TCRs are distinguishable, exhibiting dramatic increases in bond lifetime and performance relating to their structural transition rate and distance. Digital performance is best for both specificities in vitro and in vivo, but undiscernible using conventional functional avidity or TCR sequence distance metrics. Correlates of optimal biophysical parameters include magnitudes of ERK phosphorylation, CD3 surface loss, and activation marker upregulation. Our findings underscore the requirement to match TCR performance quality with pMHC copy number, as nature does. Given tumor antigen array paucity, engaging choice digital TCRs appears critical for T-cell adoptive cancer therapies and vaccines.
2024-08-21 | GSE240414 | GEO
Project description:While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCRαβ clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCRβ- versus TCRα-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.
2026-02-18 | GSE302856 | GEO
Project description:While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCR clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCR- versus TCR-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.
2026-02-18 | GSE302680 | GEO
Project description:While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCRαβ clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCRβ- versus TCRα-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.
2026-08-05 | GSE313272 | GEO
Project description:A specialized population of memory CD8+ T-cells resides in the epithelium of the respiratory tract to maintain protection against recurring infections. These cells express CD69 and the integrin αβ7 (CD103) and correspond to tissue resident memory T-cells (TRM) also described in intestine, liver and brain. A less well characterized population of CD103- CD8+ T-cells also resides in lungs and expresses markers characteristic of effector memory T-cells (TEM). We determined the transcriptional profiles of these memory CD8+ T-cell subsets retrieved from human lung resection samples and compared these with corresponding T-cell populations from peripheral blood of the same individuals. Our results demonstrate that each of the populations exhibits a distinct transcriptional identity. We found that the lung environment has a major impact on gene expression profiles. Thus, transcriptomes from CD103+ and CD103- subsets from lungs are much more resemblant to one another than to those from CD103+ or CD103- memory CD8+ T-cells from blood. TRM express specific sets of chemokine receptors, in accordance with their unique migratory properties. Furthermore, these cells constitutively express cytokine and cytotoxic genes for immediate effector function and chemokines to attract auxiliary immune cells. At the same time, multiple genes encoding inhibitory regulators are also expressed. This suggests that rapid ability to unleash effector functions is counterbalanced by programmed restraint, a combination that may be critical in the exposed but delicate tissue of the lung. Comprehensive sets of transcription factors were identified that characterize the memory CD8+ populations in the lungs. Prominent among these were components of the Notch pathway. Using mice genetically lacking expression of the NOTCH1 and NOTCH2 receptors in T-cells, we demonstrated that Notch controls both the number of lung TRM as well as the function of lung TEM. Our data illustrate the adaptation of lung resident T-cells to the requirements of the respiratory epithelial environment. Defining the molecular imprinting of these cells is important for rational vaccine design and may help to improve the properties of T-cells for adoptive cellular therapy. Material was collected from a total of 6 subjects. Three patients underwent a lobectomy for a peripheral primary lung tumor and three received lung transplantation because of end-stage pulmonary disease (COPD). Lung mononuclear cells where isolated after digestion of the partial or complete human lung resection material. Paired peripheral blood mononuclear cells were also isolated. CD8+CD16-CD56- T-cells were sorted for expression of CD103 (ITGAE). Lung and blood derived CD103+ and CD103- T-cell fractions were directly lysed after FACS sorting or stimulated overnight with antiCD3/28 beads. Due to the low frequency of resting (non-stimulated) CD103+ T-cells in peripheral blood this subset was obtained from five non-related buffy coat donors. RNA was isolated from 36 sorted cell samples and hybridized on Illumina HumanHT-12 V4.0 microarrays. Eight microarray samples (including two samples from the buffy coat donors) were excluded after hybridization since their average signal was too low.
2016-10-23 | E-GEOD-61397 | biostudies-arrayexpress
Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-?1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.
2013-04-04 | E-GEOD-43184 | biostudies-arrayexpress
Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.
2024-02-14 | PXD031794 | Pride
Project description:To evaluate the transcriptional responses of effector and memory virus-specific CD8 T cell subsets after primary and secondary influenza infection, we sorted subsets of FluNP 366-374/Db+ CD8+ T cells from the BAL, lung, and spleen at the peak of primary x31 influenza infection (day 10), resting memory (day 30), or 3 days after secondary PR8 influenza challenge (Day 30+3). Cells from the circulation were excluded from BAL and lung based on intravital labeling with anti-CD45. Memory cells from the lung were further separated in TRM and TEM subsets based on expression of CD69 at the day 30 and day 30+3 timepoints. Memory cells from the BAL were separated into long-term airway resident versus recently-recruited cells based on CD11a expression at the day 30 and days 30+3 timepoints. The results show that virus-specific BAL and lung TRM cells, but not lung TEM cells or spleen TEM cells, rapidly alter their transcriptional program and increase expression of effector molecules within 3 days of a secondary influenza challenge.
2024-02-15 | GSE247464 | GEO
Project description:Transcriptional profiling of mouse white adipose tissues. The objective of this study is to explore gene expression profiles of obese adipose tissue by DNA microarray data analysis. Male db/db (BKS.Cg-m+/+ Lepr db/J, 6 weeks old) and db/+ (BKS.Cg-Dock7m +/+ Lepr db/J, 6 weeks old) mice were used in this experiment.
2015-09-01 | E-GEOD-70527 | biostudies-arrayexpress