Determinants of the cellular immunopeptidome -cellular peptidome
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Epithelial Cell, Cell Culture
SUBMITTER: 
Assaf Kacen
LAB HEAD: Yifat Merbl
PROVIDER: PXD009935 | Pride | 2018-10-25
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| MaxQuant_Output.zip | Other | |||
| Seq51734_QE3.raw | Raw | |||
| Seq51735_QE3.raw | Raw | |||
| Seq51736_QE3.raw | Raw | |||
| Seq51737_QE3.raw | Raw |
Items per page: 5 1 - 5 of 7 |
Similar Datasets
Project description:Mass spectrometry analysis of the immunopeptidome after TNF/IFN stimulation
2018-10-22 | PXD009936 | Pride
Project description:PTM – driven antigenicity – immunopeptidome of MC38 cell line
2022-10-12 | PXD017448 | Pride
Project description:Endoplasmic reticulum aminopeptidase 1 (ERAP1) metabolizes peptides inside the ER and shapes the peptide repertoire available for binding to Major Histocompatibility Class I molecules (MHC-I). Moreover, it may have additional effects on cellular homeostasis, which have not been explored. To address these questions, we utilized genetic silencing of ERAP1 expression as well as a selective allosteric ERAP1 inhibitor to probe changes in the immunopeptidome and proteome of the A375 melanoma cancer cell line. We observed significant immunopeptidome shifts upon both methods of ERAP1 functional disruption, which were distinct for each method. Both methods of inhibition led to mild enhancement of cancer cell killing by stimulated human PBMCs from a healthy donor. ERAP1 functional disruption also resulted in significant proteomic alterations that focused on pathways related to metabolism and cellular stress. Similar proteomic changes were also observed in the leukemia cell line THP-1. Biochemical analyses suggested that ERAP1 inhibition affected ER stress, reactive oxygen species production and mitochondrial metabolism. Although the proteomics shifts were significant, their potential in shaping immunopeptidome shifts was limited since only 15.8% of differentially presented peptides belonged to proteins with altered expression and 4.8% of proteins with altered expression were represented in the immunopeptidome shifts. Taken together, our findings suggest that inhibition of ERAP1 can generate unique immunopeptidomes, primarily due to altered peptide processing in the ER, but also induce compensatory changes in the cellular proteome and metabolic state which may have additional effects on cancer cells.
2025-05-23 | PXD054491 | Pride
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:Endoplasmic reticulum aminopeptidase 1 (ERAP1) metabolizes peptides inside the ER and shapes the peptide repertoire available for binding to Major Histocompatibility Class I molecules (MHC-I). Moreover, it may have additional effects on cellular homeostasis, which have not been explored. To address these questions, we utilized genetic silencing of ERAP1 expression as well as a selective allosteric ERAP1 inhibitor to probe changes in the immunopeptidome and proteome of the A375 melanoma cancer cell line. We observed significant immunopeptidome shifts upon both methods of ERAP1 functional disruption, which were distinct for each method. Both methods of inhibition led to mild enhancement of cancer cell killing by stimulated human PBMCs from a healthy donor. ERAP1 functional disruption also resulted in significant proteomic alterations that focused on pathways related to metabolism and cellular stress. Similar proteomic changes were also observed in the leukemia cell line THP-1. Biochemical analyses suggested that ERAP1 inhibition affected ER stress, reactive oxygen species production and mitochondrial metabolism. Although the proteomics shifts were significant, their potential in shaping immunopeptidome shifts was limited since only 15.8% of differentially presented peptides belonged to proteins with altered expression and 4.8% of proteins with altered expression were represented in the immunopeptidome shifts. Taken together, our findings suggest that inhibition of ERAP1 can generate unique immunopeptidomes, primarily due to altered peptide processing in the ER, but also induce compensatory changes in the cellular proteome and metabolic state which may have additional effects on cancer cells.
2025-05-23 | PXD054494 | Pride
Project description:ER aminopeptidase 1 (ERAP1) is an ER-resident aminopeptidase that excises N-terminal residues off peptides that then bind onto Major Histocompatibility Complex I molecules (MHC-I) and indirectly modulates adaptive immune responses. ERAP1 contains an allosteric regulatory site that accommodates the C-terminus of only some peptide substrates, raising questions about its exact influence on antigen presentation and the potential of allosteric inhibition for cancer immunotherapy. We used an inhibitor that targets this regulatory site to study its effect on the immunopeptidome of a human cancer cell line. The immunopeptidomes of allosterically inhibited and ERAP1 knockout cells contain high-affinity peptides with sequence motifs consistent with the cellular HLA class I haplotypes, but were strikingly different in peptide composition. Compared to knockout cells, allosteric inhibition did not affect the length distribution of peptides and skewed the peptide repertoire both in terms of sequence motifs and HLA allele utilization, indicating significant mechanistic differences between the two ways of disrupting ERAP1 function. These findings suggest that the regulatory site of ERAP1 plays distinct roles in antigenic peptide selection, which should be taken into consideration when designing therapeutic interventions targeting the cancer immunopeptidome.
2023-11-21 | PXD039584 | Pride
Project description:HLA-I and HLA-II immunopeptidome of B cells from healthy control and Type 1 diabetics sharing similar HLA alleles.
2022-02-14 | PXD026184 | Pride
Project description:Mass spectrometry analysis of cellular targets of protein degradation
2018-10-11 | PXD009508 | Pride
Project description:Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but its effect on the repertoire of HLA Class I (HLA-I)-bound peptides presented by pancreatic β-cells is unknown. Using immunopeptidomics, we characterized the peptide/HLA-I presentation in in-vitro resting and IFN-α-exposed β-cells. IFN-α increased HLA-I expression and peptide presentation, including neo-sequences derived from alternative mRNA splicing, post-translational modifications - notably glutathionylation - and protein cis-splicing. This antigenic landscape relied on processing by both the constitutive and immune proteasome. The resting β-cell immunopeptidome was dominated by HLA-A-restricted ligands. However, IFN-α only marginally upregulated HLA-A and largely favored HLA-B, translating into a major increase in HLA-B-restricted peptides and into an increased activation of HLA-B-restricted vs. HLA-A-restricted CD8+ T-cells. A preferential HLA-B hyper-expression was also observed in the islets of T1D vs. non-diabetic donors, and islet-infiltrating CD8+ T-cells from T1D donors were reactive to some HLA-B-restricted granule peptides. Thus, the inflammatory milieu of insulitis may skew the autoimmune response toward epitopes presented by HLA-B, hence recruiting a distinct T-cell repertoire that may be relevant to T1D pathogenesis.
2025-01-08 | PXD045211 | Pride