Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Temperature induced change of the HLA ligandome

ABSTRACT: Temperature induced change of the HLA ligandome and proteome in B-cells

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Suspension Culture

SUBMITTER: Laura Demmers

LAB HEAD: Wei Wu

PROVIDER: PXD022930 | Pride | 2021-05-07

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20191217_OR14_Ag2_5607264_SA_proteome_JY_37d_24h_rep1.raw	Raw
	20191217_OR14_Ag2_5607264_SA_proteome_JY_37d_24h_rep2.raw	Raw
	20191217_OR14_Ag2_5607264_SA_proteome_JY_37d_24h_rep3.raw	Raw
	20191217_OR14_Ag2_5607264_SA_proteome_JY_37d_72h_rep1.raw	Raw
	20191217_OR14_Ag2_5607264_SA_proteome_JY_37d_72h_rep2.raw	Raw

Items per page:

1 - 5 of 47

Publications

HLA Class II Presentation Is Specifically Altered at Elevated Temperatures in the B-Lymphoblastic Cell Line JY.

Demmers Laura C LC Wu Wei W Heck Albert J R AJR

Molecular & cellular proteomics : MCP 20210429

Human leukocyte antigen (HLA) molecules play critical roles in our adaptive immune system by signaling a cell's health status to the immune system, through presentation of small peptides. Understanding HLA biology is important because of its prominent role in autoimmune diseases and cancer immunotherapy. Although both the HLA class I and class II antigen processing and presentation pathways have been studied extensively, the fundamental rules in HLA class II antigen presentation still remain les ...[more]

PMID: 33933681

Similar Datasets

The immunopeptidomic landscape of ovarian carcinoma

Project description:Immunopeptidome analysis of ovarian carcinoma tissues was performed to characterize the HLA class I and class II presented ligandome of this malignancy.

2017-11-02 | PXD007635 | Pride

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy

Project description:Anti-leukemia immunity plays an important role for disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Antigen-specific immunotherapy holds promise to strengthen immune control in CML, but requires the identification of CML-associated targets. In this study, we used a mass spectrometry-based approach to identify naturally presented HLA class I- and class II-presented peptides in 20 primary CML samples. Comparative HLA ligandome profiling using a comprehensive dataset of different hematological benign specimen delineated a novel panel of frequently expressed CML-exclusive peptides. These non-mutated target antigens are of particular relevance since our extensive data-mining approach demonstrated absence of naturally presented BCR-ABL- and ABL-BCR-derived HLA-presented peptides and the lack of frequent tumor-exclusive presentation of predescribed cancer/testis and leukemia-associated antigens. Functional characterization revealed spontaneous T-cell responses against the newly identified CML-associated peptides in CML patients and their ability to de novo induce multifunctional and cytotoxic antigen-specific T cells in healthy volunteers and CML patients. This characterizes these antigens as prime candidates for T cell-based immunotherapy approaches that may prolong TKI-free survival and even mediate cure of CML patients.

2018-12-11 | PXD010450 | Pride

Immunopeptidomics-guided warehouse design for peptide-based immunotherapy in chronic lymphocytic leukemia

Project description:In recent years the clinical success of T cell-based immunotherapy approaches has revolutionized treatment of solid tumors and hematological malignancies. However, still some patients do not respond to available therapies at all, others for limited time only. A promising low side-effect approach is peptide-based immunotherapy, which relies on specific immune recognition of tumor-associated human leucocyte antigen (HLA)-presented peptides. In this study, we developed a workflow for the immunopeptidome-guided design of off-the shelf warehouses for personalized peptide vaccines using the example of chronic lymphocyte leukemia (CLL). The so defined warehouses could provide the basis for different T cell-based immunotherapy approaches such as TCR-engineered T cell transfer or multi-peptide vaccinations. The warehouse approach enables a fast and cost-effective way to provide a personalized T cell-based immunotherapeutic approach. The here defined peptide warehouse is already utilized for a personalized multi-peptide vaccine trial (iVAC-XS15-CLL01, NCT04688385).

2021-09-10 | PXD024871 | Pride

HLA class II ligandome from HOM-2 and JY cell lines (HLA-DR an HLA-DP ligands)

Project description:A high-throughput mass spectrometry analysis was used to identify more than 16,000 cell peptides bound to several HLA-DR and -DP class II molecules isolated from large amounts of two human cell lines (HOM-2 and JY).

2021-11-03 | PXD028006 | Pride

Immunoprecipitation methods impact the peptide repertoire in immunopeptidomics

Project description:T cell-based immunotherapies, which have become a promising treatment approach for cancer patients, rely on the identification of human leukocyte antigen (HLA)-presented peptides. Mass spectrometry-based immunopeptidomics is the state-of-the-art method for the identification of clinically relevant naturally presented HLA-restricted tumor-associated antigens. In the last years, different methods for the immunoprecipitation-based isolation of HLA-presented peptides have been developed and are used in the field. Here, we performed a comparison of a column-based with a high-throughput 96-well method by analyzing the immunopeptidome of cell lines as well as primary solid and hematological tumor samples. Whereas no differences in the total number of identified peptides were observed, the column-based method identified method-exclusive peptides that featured higher hydrophobicity and exhibited improved predicted immunogenicity. Adding an additional acetonitrile elution step to the 96-well method could partially reduce this hydrophilic shift. In total, we showed that immunopeptidomics data is affected by the immunoprecipitation method used for isolation, which might have a critical impact on the selection of target antigens and has to be considered when selecting clinically relevant targets for the development of T cell-based immunotherapies.

2023-07-05 | PXD041804 | Pride

Immunopeptidome of HeLa-CIITA cells silenced for TAX1BP1(T6BP) expression

Project description:CD4+ T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented on the surface of antigen presenting cells (APCs) by the MHC-II molecules. The pathways leading to endogenous MHC-II presentation remain poorly characterized. We demonstrate here that the autophagy receptor, T6BP, influences both autophagy-dependent and -independent endogenous presentation of HIV- and HCMV-derived peptides. By studying the immunopeptidome of MHC-II molecules, we show that T6BP affects both the quantity and quality of peptides presented. T6BP silencing induces mislocalization of the MHC-II-loading compartments and a rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC-II molecules. T6BP also controls the ER localization of the chaperone calnexin that we identified as a T6BP partner. Remarkably, calnexin silencing in APCs replicates the functional consequences of T6BP silencing: decreased CD4+ T cell activation and exacerbated CD74 degradation. Altogether, we unravel T6BP as a key player of the MHC-II-restricted endogenous presentation pathway and we propose one potential mechanism of action.

2022-09-22 | PXD024417 | Pride

The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell–based immunotherapy

Project description:Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8+ T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell–based immunotherapy of MM.

2022-07-19 | PXD035324 | Pride

Pre-fractionation extends, but creates a bias in the detectable HLA class Ι ligandome

Project description:HLA class Ι molecules on the cell surface enable CD8+ T lymphocytes to recognize cellular alterations in the form of antigens, including mutations, protein copy number alterations, aberrant post-translational modifications or pathogen proteins. At any given moment, tens of thousands of different self and foreign HLA class Ι peptide ligands may be presented on the cell surface by MHC class Ι complexes. Analysis of the HLA ligandome thrusts therefore unique challenges due to their enormous biochemical diversity and inherently wide range of abundances. Despite advances in enrichment, separation, MS instrumentation and fragmentation, it is still not achievable to cover the HLA class Ι ligandome in sufficient depth to support routine identification of e.g. viral pathogens or immuno-therapeutically important tumor neo-antigens. In this study, we evaluate two pre-fractionation techniques, high pH reversed phase and strong cation exchange for complementary analysis of HLA class Ι peptide ligands, benchmarking them against analyses circumventing pre-fractionation. We observe that pre-fractionation substantially extends the detectable HLA class Ι ligandome, but also creates an identification bias. We advocate a rational choice between no-fractionation, high pH reversed phase or strong cation exchange pre-fractionation for deeper HLA class Ι ligandome analysis depending on the targeted HLA locus, allele or peptide ligand modification

2019-02-25 | PXD011257 | Pride

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

Project description:Immunotherapies targeting cancer-specific neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies synergize with immunotherapies, mediated bythe de-repression of endogenous retroviral element (ERV)-encoded promoters, and the initiation of transcription. Here, we use deep RNA sequencing from cancer cell lines treated with DNA methyltransferase inhibitors (DNMTi) and/or Histone deacetylase transferase inhibitors (HDACi), to assemble a de novo transcriptome and identified 3,023 ERV-derived, treatment-induced novel polyadenylated transcripts (TINPATs), encoding for 61,426 open reading frames. Using Immunopeptidomics, we further demonstrate the human leukocyte antigen (HLA) presentation of treatment-induced neoepitopes (t-neoepitopes) derived from TINPATs. We illustrate the potential of the identified t-neoepitopes to elicit a T-cell response and cancer cell killing. The presence of t-neoepitopes was further verified in AML patient samples 48/96 h after in vivo treatment with the DNMT inhibitor Decitabine. Our findings highlight a novel mechanism of ERV-derived neoantigens in epigenetic and immune therapies.

2023-08-18 | PXD035750 | Pride

Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors.

Project description:Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS-tumors of infancy and early childhood. Hallmark is the surprisingly simple genomics with a truncating mutation in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T-cells. However, it is unclear, what T-cells might recognize on AT/RT cells. Here, we report a comprehensive analysis of naturally presented HLA-class-I and class-II ligands on n=23 AT/RTs. MS-based analysis of the HLA-ligandome revealed 55 class-I and 139 class-II peptides from tumor-associated proteins.

2022-05-31 | PXD033935 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data