Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA150755 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MHC I-peptides (MIPs) play an essential role in normal homeostasis and diverse pathological conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and whose physical nature remains elusive. We used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and -B molecules on human EBV-infected B lymphocytes from four subjects. We found that although HLA-different subjects present different MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biological pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved vs. polymorphic genomic sequences, derived preferentially from abundant transcripts and conveyed to the cell surface a cell type-specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, while MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which i) the generation of MIPs by a transcript depends on its abundance and DRiP rate, and ii) the DRiP rate is regulated to a large extent by miRNAs. We performed genome-wide miRNA expression profiling of B cells and non-lymphoid cells to confirm that miRNAs predicted to regulate transcripts source of MHC I-associated peptides are expressed in a cell-specific manner. miRNA profiling was done on (i) 4 B-lymphoblastoid cell lines (B-LCLs) obtained from the peripheral blood mononuclear cells of 4 subjects, (ii) CD19+CD20- B cells and CD19+CD20+ B cells of one of the subjects, (iii) HeLa cells, and (iv) HEK293 cells.
2012-03-25 | E-GEOD-35319 | biostudies-arrayexpress
Project description:MHC I-peptides (MIPs) play an essential role in normal homeostasis and diverse pathological conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and whose physical nature remains elusive. We used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and -B molecules on human EBV-infected B lymphocytes from four subjects. We found that although HLA-different subjects present different MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biological pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved vs. polymorphic genomic sequences, derived preferentially from abundant transcripts and conveyed to the cell surface a cell type-specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, while MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which i) the generation of MIPs by a transcript depends on its abundance and DRiP rate, and ii) the DRiP rate is regulated to a large extent by miRNAs. We performed genome-wide miRNA expression profiling of B cells and non-lymphoid cells to confirm that miRNAs predicted to regulate transcripts source of MHC I-associated peptides are expressed in a cell-specific manner.
2012-03-25 | GSE35319 | GEO
Project description:Using highthroughput mass spectrometry, we probed the sixreadingframe translation of human B cells’ transcriptome. We report that about 10% of MHC Iassociated peptides (MAPs) derive from noncanonical reading frames. These socalled cryptic MAPs originate from allegedly non- coding genomic sequences and from outofframe translation. Their biogenesis and properties differ in many ways from those of conventional MAPs. Thus, cryptic MAPs come from very short proteins with atypical Ctermini, and they are coded by transcripts bearing long UTRs selectively enriched in destabilizing elements. Cryptic MAPs increase the complexity of the immunopeptidome and represent an heretofore unexploited source of potential tumorspecific epitopes. In a more general context, the features of cryptic MAPs suggest that mRNA instability is instrumental in the biogenesis of MAPs. Associated RNA-seq accession: GSE67174 .
2016-01-28 | PXD001898 | Pride
Project description:In an effort to understand the differences between the presented repertoire of MHC-I peptides in healthy lung tissue and tumor bearing lung, we evaluated the translatome of AT2 cells and tumor cells.
2022-07-08 | GSE178944 | GEO
Project description:The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. We have purified MHC class-I and MHC-II peptides and analysed them by mass spectrometry. We have successfully identified 97 mycobacterial peptides presented by MHC-II and 54 presented by MHC-I, from 76 and 41 antigens, respectively. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cells from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying novel candidate antigens.
2020-01-08 | E-MTAB-8057 | biostudies-arrayexpress
Project description:Piwi-interacting RNAs (piRNAs) are ~24-30 nucleotide regulatory RNAs that are abundantly expressed in gonads. The most well-understood piRNAs mediate post-transcriptional defense against transposable elements (TEs), and derive from sense or antisense strands as a consequence of "ping-pong" amplification of complementary sequences of active TEs and piRNA master control transcripts. Another class of piRNAs, such as those expressed in pachytene testis, derive from large intergenic clusters that are strictly single-stranded. Here, we report a third substrate that generates abundant primary piRNAs. In somatic follicle cells of Drosophila ovaries, we cloned >1 million piRNAs from thousands of messenger RNAs, and these were quite preferentially derived from 3' untranslated regions. This segregation implies a competition between the translation machinery and primary piRNA biogenesis machinery for mRNA access. 3 replicates.
2010-01-03 | E-GEOD-15825 | biostudies-arrayexpress
Project description:In this study, primary human monocyte-derived macrophages were exposed to plant-derived virus-like particles (VLPs) bearing influenza A hemagglutinin (HA) or soluble influenza HA, as control. Immunopurified MHC class I-associated peptides were analysed by nano-flow high pressure liquid chromatography coupled to high-resolution dopant-assisted electrospray ionisation mass spectrometry. A total of 109 host-derived MHC I peptides were identified in the VLP-treated samples, two of which were also detected in controls. The peptides unique to VLP treatment were, on average, ~13 amino acid residues long, more basic and hydrophilic, and were mainly processed via proteolysis by matrix metalloproteinases and cathepsins. The proteins associated with these peptides were primarily involved in cellular, metabolic and regulatory processes and activated several pathways including inflammation stimulation and attenuation, response to stimuli, innate and adaptive immunity, clathrin-mediated endocytosis, protein synthesis and endo-lysosomal degradation. This study is the first report to describe the response of a primary human antigen-presenting cell to nanoparticulate vs. soluble antigen exposure from an immunopeptidomics point of view.
2022-02-24 | PXD010741 | Pride
Project description:Immunogenic cell death (ICD) in cancer represents a functionally unique therapeutic response that can induce tumor-targeting immune responses. ICD is characterized by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which confer adjuvanticity to dying cancer cells. The spatiotemporally defined emission of DAMPs during ICD has been well described; whereas the epigenetic mechanisms that regulate ICD hallmarks have not yet been deeply elucidated. Here, we aimed to examine the involvement of miRNAs and their putative targets taking advantage from well-established in vitro models of ICD. To this end, B cell lymphoma (Mino) and breast cancer (MDA-MB-231) cell lines were exposed to two different ICD inducers: the combination of retinoic acid (RA) and interferon-alpha (IFN-a) and doxorubicin, and to non ICD inducers like gamma irradiation. Then, miRNA and mRNA profiles were studied by next generation sequencing. Co-expression analysis identified 16 miRNAs differentially modulated in cells subjected to ICD. Integrated miRNA-mRNA functional analysis revealed candidate miRNAs, mRNAs, and modulated pathways associated with Immune System Process (GO Term). In this sense, ICD induced a distinctive transcriptional signature hallmarked by regulation of antigen presentation, a crucial step for a proper immune system antitumor response activation. Interestingly, the major histocompatibility complex class I (MHC-I) pathway was upregulated whereas class II (MHC-II) was downregulated. Analysis of MHC-II associated transcripts and HLA-DR surface expression validated the inhibition of this pathway by ICD on lymphoma cells. miR-4284 and miR-212-3p were the strongest miRNAs upregulated by ICD associated with this event. It is well known that MHC-II expression on tumor cells facilitates the recruitment of CD4+ T cells. However, the interaction between tumor MHC-II and the inhibitory co-receptor LAG-3 on tumor-associated lymphocytes could provide an immunosuppressive signal that directly represses effector cytotoxic activity. In this context, MHC-II downregulation by ICD could enhance antitumor immunity. Overall, we found that the miRNA profile was significantly altered during ICD. Several miRNAs are predicted to be involved in the regulation of Class I and II MHC pathway, whose implication in ICD was demonstrated herein for the first time, which could eventually modulate tumor recognition and attack by the immune system.
2022-08-08 | E-MTAB-11799 | biostudies-arrayexpress
Project description:The central nervous system (CNS), despite the presence of strategically positioned anatomical barriers designed to protect it, is not entirely isolated from the immune system. In fact, it remains physically connected to and can be influenced by the peripheral immune system. How the CNS retains such responsiveness while maintaining “immune privilege” remains an outstanding conundrum. In searching for molecular cues that derive from the CNS and allow its direct communication with the immune system, we discovered a repertoire of CNS-derived endogenous guardian peptides presented on major histocompatibility complex (MHC) II molecules at the CNS borders. During homeostasis, a preponderance of these guardian peptides were found to be bound to MHC II molecules throughout the path of lymphatic drainage from the brain to its surrounding meninges and its draining cervical lymph nodes. With neuroinflammatory disease, however, the presentation of guardian peptides was diminished. Fascinatingly, boosting the presence of these guardian peptides reinforced a population of suppressor CD4+ T cells and significantly reduced CNS autoimmune disease. This unexpected discovery of CNS-derived autoimmune guardian peptides may be the molecular key adapting the CNS to receive information and to maintain continuous dialogue with the immune system while balancing overt autoreactivity. This sheds new light on how we conceptually think about and therapeutically target neuroinflammatory and neurodegenerative diseases.
2024-10-11 | GSE240691 | GEO
Project description:A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes-associated b57 polymorphism. We generated knock-in Non-obese Diabetic (NOD) mice with a single amino acid change in the CLIP segment of invariant chain in order to moderately slow CLIP dissociation from I-Ag7. These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within b cell secretory granules. Rapid CLIP dissociation enhanced presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition.
2018-08-09 | GSE118322 | GEO