Ontology highlight
ABSTRACT:
PROVIDER: PRJEB34209 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3504830_1.fastq.gz | Fastqsanger.gz | |||
| ERR3504830_2.fastq.gz | Fastqsanger.gz | |||
| ERR3504831_1.fastq.gz | Fastqsanger.gz | |||
| ERR3504831_2.fastq.gz | Fastqsanger.gz | |||
| ERR3504832_1.fastq.gz | Fastqsanger.gz |
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Project description:We employed PeptiCHIP Immunopeptidomics to profile tumor associated antigens (TAA) actively targeted by tumor specific T cells by exploiting the trogocytosis effect, whereby antigen presenting cells (APCs) nibble portions of the cognate T cell containing the TCR. The antigen presenting cells were then processed by Immunoaffinity purification by peptiCHIP to identify the relevant HLA-I peptides by LCMS on the Bruker Tims TOF Pro instrument.
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Project description:Expression data from antigen-presenting cells (APCs)
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Project description:Cross-presentation of exogenous antigens in HLA-class I molecules by professional antigen presenting cells (APCs) is crucial for CD8+ T cell function. Recent murine studies show that several non-professional APCs, including cancer-associated fibroblasts (CAFs) also possess this capacity. It is currently unknown whether human CAFs are able to cross-present exogenous antigen, which molecular pathways are involved in this process and how this ultimately affects tumor-specific CD8+ T cell function. Here we show that human colorectal cancer (CRC)-derived CAFs display an enhanced capacity to cross-present neoantigen-derived synthetic long peptides (SLPs) when compared to normal colonic fibroblasts. Importantly, cross-presentation of antigens required the lysosomal protease Cathepsin S. Cathepsin S expression by CAFs was detected in situ in human CRC tissue, was upregulated in ex vivo cultured CRC-derived CAFs and showed increased expression in normal fibroblasts after exposure to CRC-conditioned medium. Cognate interaction between CD8+ T cells and cross-presenting CAFs suppressed T cell function, reflected by decreased cytotoxicity, reduced activation (CD25, CD137) and increased exhaustion (TIM3) marker expression. Our data indicate that CAFs may directly suppress tumor-specific T cell function in an antigen-dependent fashion in human CRC.
2022-03-03 | PXD029507 | Pride
Project description:Dengue virus (DENV) causes widespread mosquito-borne infection. While most symptomatic patients experience mild disease, a fraction progresses to severe dengue (SD)--a life-threatening condition whose pathogenesis remains largely unknown. We integrated virus-inclusive single cell RNA-Seq 2 (viscRNA-Seq 2) with functional assays to determine the immunological hallmarks of SD progression in children’s blood. We show that beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell abundance, gene and protein expression and secretion, and cell-cell communications suggesting increased migration and inflammation in SD progressors, yet concurrent: i) impaired interferon responses and antigen presentation, in part DENV-modulated, by antigen presenting cells (APCs) in face of intact uptake; ii) activation, regulation, and exhaustion of effector responses, enhanced IFNγ-responses, and appearance of HLA-DR-expressing NK cells possibly compensating for APCs impairments. These observations reveal the target cells of DENV in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.
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Project description:P25 is the major T cell epitope for Ag85B and enables them to induce P25-specific CD4+ Th1 cells. We used microarrays to examine the gene expression of antigen-presenting cells (APCs) stimulated with P25 and P25-specific CD4+ T cells. Splenic APCs from WT mice were cultured with P25 or medium in the presence of P25 TCR CD4+ T cells. After overnight culture, these APCs were enriched and total RNA was prepared using RNeasy (QIAGEN) according to the manufacturer's instructions. Mixed total RNA from three independent experiments was used for microarray analysis.
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Project description:Increasing evidence indicates CD4+ T cells can recognize cancer-specific antigens and control tumor growth. However, it remains difficult to predict the antigens that will be presented by human leukocyte antigen class II molecules (HLA-II) - hindering efforts to optimally target them therapeutically. Obstacles include inaccurate peptide-binding prediction and unsolved complexities of the HLA-II pathway. To address these challenges, we introduce an improved technology for discovering HLA-II binding motifs and conduct a comprehensive analysis of tumor-ligandomes to learn processing rules relevant in the tumor microenvironment (TME). We profiled HLA-II alleles and showed that binding motifs are highly sensitive to HLA-DM, a peptide loading chaperone. We also revealed that intratumoral HLA-II presentation is dominated by professional antigen presenting cells (APCs), rather than cancer cells. Integrating these observations, we developed algorithms that accurately predict APC ligandomes, including peptides from phagocytosed cancer cells. These tools and biological insights will enhance HLA-II directed cancer therapies.
2019-06-18 | MSV000083991 | MassIVE
Project description:Immune evasion is an important hallmark of cancer ensured by diverse strategies, including immunosuppression and downregulation of antigen presentation. Here, to restore immunogenicity of cancer cells, we employed the minimal gene regulatory network of highly immunogenic type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen presenting cells (APCs). We showed that enforced expression of PU.1, IRF8 and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 33 cell lines derived from human and mouse hematological and solid tumors. PIB gradually modified the cancer cell transcriptional and epigenetic program imposing global antigen presentation and cDC1 gene signatures within 9 days. cDC1 reprogramming restored the expression of antigen presentation complexes as well as co-stimulatory molecules at the cell surface, leading to the presentation of endogenous antigens on MHC-I, and to CD8+ T cell mediated killing. Functionally, tumor- APCs acquired the ability to uptake and process exogenous proteins and dead cells, secreted inflammatory cytokines and cross-presented antigens to naïve CD8+ T cells. Importantly, tumor-APCs were efficiently generated at the single cell level from primary cancer cells of 7 solid tumors that presented antigens to memory and naïve T-cells, as well as to activated patient-specific intra-tumoral lymphocytes. Alongside antigen presentation, tumor-APCs harboring TP53, KRAS and PTEN mutations showed impaired tumorigenicity in vitro and in vivo. Finally, using in vivo mouse models of melanoma, we showed that intra-tumoral injection of tumor-APCs promoted lymphoid infiltration, delayed tumor growth and increased survival. The anti-tumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors enabling tumor eradication. Our approach combines cDC1’s antigen processing and presenting abilities with endogenous generation of tumor antigens and serves as a platform for the development of novel immunotherapies based on endowed antigen presentation in cancer cells.
2023-10-24 | PXD039789 | Pride
Project description:Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen- presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surface of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I, and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross- presented antigens to naïve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.
2023-07-07 | GSE200341 | GEO
Project description:The peptides repertoire presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules, referred to as the MHC I-associated peptidome (MIP), regulates all critical events that occur during the lifetime of CD8+ T cells. The MIP presented by thymic antigen presenting cells (APCs) is crucial for shaping CD8+ T cell repertoire and self-tolerance, while the MIP presented by peripheral tissues and organs is not only involved in maintaining periphery CD8+ T cell survival and homeostasis, but also mediates immune surveillance and autoimmune responses of CD8+ T cells under pathological conditions. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the destruction pancreatic β cells, mediated primarily by autoreactive CD8+ T cells. Non-obese diabetic (NOD) mouse is one of important animal models of spontaneous autoimmune diabetes that shares several key features with human T1D. Here, we deeply analyzed the MIP derived from the primary tissues of thymus and pancreas in NOD mice using targeted database searches of mass spectrometry data. We demonstrated that the thymus MIP source proteins accommodated only a small portion of the transcriptome of thymus epithelial cells, and partially shared with the MIP source proteins derived from NOD mice pancreas and β cell line. The global view of the MHC I-associated self-peptides repertoire in the thymus and pancreas of NOD mice may serve as a biological reference to identify potential autoantigens targeted by autoreactive CD8+ T cells in T1D.
2022-10-14 | PXD031966 | Pride
Project description:CD4+ T cells recognize peptide antigens presented on class II Major Histocompatibility Complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor (TCR) sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4+ T cells challenging. We have expanded our platform of Signaling and Antigen-presenting Bifunctional Receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4+ cell antigen discovery. SABR-IIs can present epitopes to CD4+ T cells and induce signaling upon their recognition, allowing a readable output. Here, we demonstrate that SABR-IIs libraries presenting endogenous and non-contiguous epitopes can be used for antigen discovery. Using SABR-II libraries in conjunction with single cell RNA sequencing, we de-convoluted multiple highly expanded TCRs from pancreatic islets of Non-Obese Diabetic (NOD) mice and identified novel Hybrid Insulin Peptide targets. We compounded antigen discovery by incorporating computational TCR similarity prediction metrics followed by experimental validation. Finally, we showed SABR-IIs presenting epitopes in class II Human Leukocyte Antigen (HLA-II) alleles can be used for antigen discovery for human CD4+ T cells. Taken together, we have developed a rapid, flexible, scalable, and versatile approach for de novo identification of CD4+ T cell ligands from single cell RNA sequencing data using experimental and computational approaches.
2024-02-19 | GSE247410 | GEO