PXD004746

PXD004746 is an original dataset announced via ProteomeXchange.

Title	Antigen Presentation Profiling Reveals T-cell Recognition of Lymphoma Immunoglobulin Neoantigens
Description	Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. Such neoantigens have been implicated in response to immunotherapies including immune checkpoint blockade, yet their identification and validation remains challenging. Here we discover neoantigens in human mantle cell lymphomas using an integrated strategy for genomic and proteomic tumor antigen discovery that interrogates peptides presented within the tumor major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically identify neoantigen peptides in diagnostic tumor specimens from 17 patients. Remarkably, the 52 discovered neoantigenic peptides were invariably derived from the lymphoma immunoglobulin (Ig) heavy or light chain variable regions. Although we could identify MHC presentation of private germline polymorphic alleles, no mutated peptides were recovered from non-Ig somatically mutated genes. The immunoglobulin variable region somatic mutations were almost exclusively presented by MHC-II. We found T-cells specific for an immunoglobulin-derived neoantigen in the blood of a patient using MHC-II tetramers, and these T-cell clones expanded in frequency following tumor vaccination. These results demonstrate that an integrative approach combining MHC isolation, peptide identification and exome sequencing is an effective platform to uncover tumor neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2017-03-27
AnnouncementXML	Submission_2017-03-27_01:45:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Niclas Olsson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-10 03:20:09	ID requested
⏵ 1	2017-03-27 01:46:00	announced

Khodadoust MS, Olsson N, Wagar LE, Haabeth OA, Chen B, Swaminathan K, Rawson K, Liu CL, Steiner D, Lund P, Rao S, Zhang L, Marceau C, Stehr H, Newman AM, Czerwinski DK, Carlton VE, Moorhead M, Faham M, Kohrt HE, Carette J, Green MR, Davis MM, Levy R, Elias JE, Alizadeh AA, Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens. Nature, 543(7647):723-727(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Human, mantle cell lymphoma, antigen presentation, MHC, LTQ Orbitrap Elite

Joshua E Elias
contact affiliation	Department of Chemical & Systems Biology Stanford University USA
contact email	josh.elias@stanford.edu
lab head
Niclas Olsson
contact affiliation	Stanford University
contact email	nolsson@stanford.edu
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/2017/03/PXD004746

PRIDE project URI

• PRIDE
  1. PXD004746
     1. Label: PRIDE project
     2. Name: Antigen Presentation Profiling Reveals T-cell Recognition of Lymphoma Immunoglobulin Neoantigens