PXD035324

PXD035324 is an original dataset announced via ProteomeXchange.

Title	The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell–based immunotherapy
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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:44.840.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jens Bauer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-14 04:51:14	ID requested
1	2022-07-19 10:26:36	announced
⏵ 2	2023-11-14 08:57:46	announced	2023-11-14: Updated project metadata.

Walz S, Stickel JS, Kowalewski DJ, Schuster H, Weisel K, Backert L, Kahn S, Nelde A, Stroh T, Handel M, Kohlbacher O, Kanz L, Salih HR, Rammensee HG, Stevanovi, ć S, The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy. Blood, 126(10):1203-13(2015) [pubmed]

submitter keyword: human leukocyte antigens, t-lymphocytes, mass spectrometry, immunotherapy, ligands, peptides,antigens, multiple myeloma

Juliane Walz
contact affiliation	Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany
contact email	Juliane.Walz@med.uni-tuebingen.de
lab head
Jens Bauer
contact affiliation	Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
contact email	j.bauer@uni-tuebingen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/07/PXD035324

PRIDE project URI

• PRIDE
  1. PXD035324
     1. Label: PRIDE project
     2. Name: The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell–based immunotherapy