PXD056426 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Deleterious knock-outs in the HLA class I antigen processing and presentation machinery induce distinct changes in the immunopeptidome |
Description | The human leukocyte antigen (HLA) processing and presentation machinery (APPM) is altered in various diseases and in response to drug treatments. Defects in the machinery may change presentation levels or alter the repertoire of presented peptides, globally or in an HLA allele restricted manner, with direct implications for adaptive immunity. In this study, we investigated the immunopeptidome landscape across a panel of isogenic HAP1 cell line clones each with a knock-out of a single gene encoding a key protein in the APPM, including B2M, TAP1, TAP2, TAPBP, IRF2, PDIA3, ERAP2, GANAB, SPPL3, CANX, and CALR. We applied immunopeptidomics and proteomics methods to assess the successful gene knock-outs on the protein level, to understand how these proteins participate in antigen presentation, and to contextualize protein expression and antigen presentation. The knocked-out proteins were clearly absent in the respective samples. We find that knocking-out an APPM component leads to the presentation of a subset of peptides that are normally presented on the control wild type cells. We assessed the immunopeptidomes qualitatively and quantitatively, considering factors like peptide diversity, peptide length distribution, and binding affinity to the endogenously expressed HLA alleles in HAP1 cells. We demonstrated a prominent HLA allele-specific alterations in several knock-out conditions. For CALR, CANX, and TAP1, HLA allele-related significant change in presentation level was found for A*02:01 and as well as B*40:01. Overall, this work represents a first systematic analysis of the effect of a panel of single APPM knock-out clones from a single cell line in a controlled environment. This approach could facilitate the creation of predictive tools capable of prioritizing HLA-bound peptides likely to be presented when presentation defects occur, such as in cancer and viral infections. |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-04 |
AnnouncementXML | Submission_2025-04-04_13:09:21.154.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Michal Bassani-Sternberg |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-10-01 07:44:17 | ID requested | |
⏵ 1 | 2025-04-04 13:09:21 | announced | |
Publication List
Keyword List
ProteomeXchange project tag: Human Immuno-Peptidome Project (HUPO-HIPP) (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project |
submitter keyword: Immunopeptidomics, antigen presentation |
Contact List
Michal Bassani-Sternberg |
contact affiliation | Department of oncology UNIL CHUV Ludwig Institute for Cancer Research Lausanne Office B25A/04/94 Rue du Bugnon 25a, CH-1005 Lausanne |
contact email | michal.bassani@chuv.ch |
lab head | |
Michal Bassani-Sternberg |
contact affiliation | UNIL/CHUV |
contact email | michal.bassani@chuv.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD056426
- Label: PRIDE project
- Name: Deleterious knock-outs in the HLA class I antigen processing and presentation machinery induce distinct changes in the immunopeptidome