Ontology highlight
ABSTRACT:
PROVIDER: PRJNA655753 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12404766.fastq.gz | Fastqsanger.gz | |||
| SRR12404766_1.fastq.gz | Fastqsanger.gz | |||
| SRR12404766_2.fastq.gz | Fastqsanger.gz | |||
| SRR12404767.fastq.gz | Fastqsanger.gz | |||
| SRR12404767_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFNγ resulted in a remarkable remoulding of the immunopeptidome, with only a 34% overlap between untreated and treated cells across the HLA-I immunopeptidome, and expression of HLA-II only on treated cells. IFNγ increased the overall number, diversity and abundance of the immunopeptidome, as well as the proportion of coverage of source antigens. The suite of peptides displayed under conditions of IFNγ treatment included many known tumour associated antigens, with the HLA-II repertoire sampling 265 breast cancer associated antigens absent from those sampled by HLA-I. Quantitative analysis of the transcriptome (10,248 transcripts) and proteome (6783 proteins) of these cells revealed 229 proteins and transcripts were commonly differentially expressed, most of which involved in downstream targets of IFNγ signalling including components of the antigen processing machinery such as tapasin and HLA. However, these changes in protein expression did not explain the dramatic modulation of the immunopeptidome following IFNγ treatment. These results demonstrate the high degree of plasticity in the immunopeptidome TNBC cells following cytokine stimulation and provide evidence that under pro-inflammatory conditions a greater variety of HLA-I and HLA-II vaccine targets are unveiled to the immune system. This has important implications for the development of personalised cancer vaccination strategies.
2021-04-01 | GSE163067 | GEO
Project description:Post-translational spliced peptides
| PRJEB53723 | ENA
Project description:Post translational spliced peptides bound to the HLA are unique type of peptides, shown in cancer, for HLA-class-I. Thus far, no consensus has been reached on the extent to which post-translational spliced peptides (PTSPs) occur, stirring significant debate. Furthermore, the role of the HLA-class-II pathway has been studied only in diabetes. Here, we exploit our large-scale cancer peptidomics database and devise a pipeline to filter spliced peptide predictions, to identify recurring spliced peptides, both for HLA-class-I and -II. Our results indicate that HLA-Class-I spliced peptides account for a low percentage (4.4%) of the immunopeptidome, yet are larger in number relative to other types of identified aberrant peptides. Therefore, spliced peptides contribute significantly to the repertoire of presented peptides in cancer cells. In addition, HLA-class-II bound spliced peptides were identified as well, but to a lower extent (0.6%).
2023-05-10 | PXD034788 | Pride
Project description:The identification of peptides presented by HLA class I molecules to CD8+ T cells – i.e. the HLA-I immunopeptidome - is a useful tool to fish epitopes suitable for vaccinations and immunotherapies against cancer, infection and autoimmunity. These peptides are mainly generated by proteasomes through peptide hydrolysis and peptide splicing. Post-translationally spliced epitopes can enlarge the antigenic landscape and thus immunotherapy efficacy. Their identification is challenging, and the few methods proposed so far hinted toward a controversial broad spectrum of cis-spliced peptide frequencies in HLA-I immunopeptidomes. We here developed a new method named SPI-ART, which can identify cis-spliced peptides in HLA-I immunopeptidomes with precision and recall outperforming all other methods. The benchmark of the methods’ performances provided the proper analytical framework to explain the discordant results published so far. It also allowed to estimate the frequency of cis-spliced peptides in HLA-I immunopeptidomes, and to shed light on the biochemistry of these unconventional peptides and their potential antigenicity.
2022-08-12 | PXD025346 | Pride
Project description:The diversity of peptides displayed by class I HLA plays an essential role in T cell immunity. The peptide repertoire is extended by various post-translational modifications, including cis-splicing of peptides from the same protein. Here, we have applied a novel bioinformatic workflow and demonstrate that spliced-peptides are also generated through trans-splicing (fusion of peptide segments from distinct antigens) and their abundance challenges current models of proteasomal-splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA binding motif sequence features. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design and immunotherapy.
2021-12-06 | PXD017922 | Pride
Project description:The diversity of peptides displayed by class I HLA plays an essential role in T cell immunity. The peptide repertoire is extended by various post-translational modifications, including cis-splicing of peptides from the same protein. Here, we have applied a novel bioinformatic workflow and demonstrate that spliced-peptides are also generated through trans-splicing (fusion of peptide segments from distinct antigens) and their abundance challenges current models of proteasomal-splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA binding motif sequence features. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design and immunotherapy.
2018-10-16 | PXD009660 | Pride
Project description:Peptides generated by proteasome-catalyzed splicing of non-contiguous amino acid sequences have been shown to constitute a source of non-templated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of human immunodeficiency virus type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly-applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I-bound peptides on HIV-infected cells. We demonstrate that HIV-1-derived spliced peptides comprise a novel, but relatively minor, component of the HLA-I-bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8+ T cell responses relatively infrequently during infection, CD8+ T cells primed by partially-overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically under-utilized during natural infection.
2019-11-25 | PXD015489 | Pride
Project description:Peptide vaccination remains a viable approach to induce T-cell mediated killing of tumours. To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFNγ resulted in a remarkable remoulding of the immunopeptidome, with only a 34% overlap between untreated and treated cells across the HLA-I immunopeptidome, and expression of HLA-II only on treated cells. IFNγ increased the overall number, diversity and abundance of the immunopeptidome, as well as the proportion of coverage of source antigens. The suite of peptides displayed under conditions of IFNγ treatment included many known tumour associated antigens, with the HLA-II repertoire sampling 265 breast cancer associated antigens absent from those sampled by HLA-I. Quantitative analysis of the transcriptome (10,248 transcripts) and proteome (6783 proteins) of these cells revealed 229 proteins and transcripts were commonly differentially expressed, most of which involved in downstream targets of IFNγ signalling including components of the antigen processing machinery such as tapasin and HLA. However, these changes in protein expression did not explain the dramatic modulation of the immunopeptidome following IFNγ treatment. These results demonstrate the high degree of plasticity in the immunopeptidome TNBC cells following cytokine stimulation and provide evidence that under pro-inflammatory conditions a greater variety of HLA-I and HLA-II vaccine targets are unveiled to the immune system. This has important implications for the development of personalised cancer vaccination strategies.
2021-05-13 | PXD023044 | Pride
Project description:Peptide vaccination remains a viable approach to induce T-cell mediated killing of tumours. To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFNγ resulted in a remarkable remoulding of the immunopeptidome, with only a 34% overlap between untreated and treated cells across the HLA-I immunopeptidome, and expression of HLA-II only on treated cells. IFNγ increased the overall number, diversity and abundance of the immunopeptidome, as well as the proportion of coverage of source antigens. The suite of peptides displayed under conditions of IFNγ treatment included many known tumour associated antigens, with the HLA-II repertoire sampling 265 breast cancer associated antigens absent from those sampled by HLA-I. Quantitative analysis of the transcriptome (10,248 transcripts) and proteome (6783 proteins) of these cells revealed 229 proteins and transcripts were commonly differentially expressed, most of which involved in downstream targets of IFNγ signalling including components of the antigen processing machinery such as tapasin and HLA. However, these changes in protein expression did not explain the dramatic modulation of the immunopeptidome following IFNγ treatment. These results demonstrate the high degree of plasticity in the immunopeptidome TNBC cells following cytokine stimulation and provide evidence that under pro-inflammatory conditions a greater variety of HLA-I and HLA-II vaccine targets are unveiled to the immune system. This has important implications for the development of personalised cancer vaccination strategies.
2021-05-13 | PXD023038 | Pride
Project description:T cell-mediated immunity seems to play a critical role against SARS-CoV-2 infection and establishing protective memory. Yet the repertoire of viral epitopes responsible for activation of T cell responses remains mostly unknown. Identification and characterization of viral peptides presented on class I human leukocyte antigen (HLA-I) will reveal the viral signatures as seen by cytotoxic T cells that can then be harnessed for the development of effective vaccines. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two human cell lines at different times post-infection using mass spectrometry. We found HLA-I peptides derived not only from canonical ORFs, but also from internal out-of-frame ORFs in Spike and Nucleoprotein not currently captured by vaccine approaches. Whole proteome analysis revealed that expression of ubiquitination pathway proteins, and the proteasome maturation protein, POMP, were significantly altered in infected cells. Retrospective analysis of computational predictions highlighted shortcomings of in silico-only approaches in recovering the observed viral epitopes. Finally, given the experimental evidence for endogenous processing and presentation of the viral peptides we detected, we estimated that at least one HLA-A, -B, or -C allele is covered by at least one peptide for 99% of the population. These biological insights and the list of naturally presented SARS-CoV-2 peptides will facilitate data-driven selection of peptides for immune monitoring and vaccine development.
2020-10-08 | GSE159191 | GEO