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PXD005704 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAntigen Presentation Profiling Reveals T-cell Recognition of Lymphoma Immunoglobulin Neoantigens
DescriptionCancer 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 and several cell lines. Remarkably, the 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNiclas Olsson
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; deamidated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-01-15 09:29:50ID requested
12017-03-27 00:54:52announced
Publication List
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]
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: Human, LTQ Orbitrap Elite, antigen presentation, MHC class I
Contact List
Joshua E Elias
contact affiliationDepartment of Chemical & Systems Biology, Stanford University, USA
contact emailjosh.elias@stanford.edu
lab head
Niclas Olsson
contact affiliationStanford University
contact emailnolsson@stanford.edu
dataset submitter
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Dataset FTP location
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