PXD015489

PXD015489 is an original dataset announced via ProteomeXchange.

Title	Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection
Description	Peptides generated by proteasome-catalyzed splicing of non-contiguous amino acid sequences have been shown to constitute a source of non-templated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of human immunodeficiency virus type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly-applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I-bound peptides on HIV-infected cells. We demonstrate that HIV-1-derived spliced peptides comprise a novel, but relatively minor, component of the HLA-I-bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8+ T cell responses relatively infrequently during infection, CD8+ T cells primed by partially-overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically under-utilized during natural infection.
HostingRepository	PRIDE
AnnounceDate	2019-11-25
AnnouncementXML	Submission_2019-11-25_03:43:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicola Ternette
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: HIV-1 vector pNL4-3; NCBI TaxID: 151458;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-17 07:58:58	ID requested
⏵ 1	2019-11-25 03:43:43	announced

Paes W, Leonov G, Partridge T, Chikata T, Murakoshi H, Frangou A, Brackenridge S, Nicastri A, Smith AG, Learn GH, Li Y, Parker R, Oka S, Pellegrino P, Williams I, Haynes BF, McMichael AJ, Shaw GM, Hahn BH, Takiguchi M, Ternette N, Borrow P, T cells in HIV-1 infection. Proc Natl Acad Sci U S A, 116(49):24748-24759(2019) [pubmed]

submitter keyword: Peptide splicing, spliced epitope, proteasome, human leukocyte antigen, immunopeptidome, CD8+ T cell, human immunodeficiency virus, viral escape, mass spectrometry, epitope discovery

Nicola Ternette
contact affiliation	Nuffield Department Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom.
contact email	nicola.ternette@ndm.ox.ac.uk
lab head
Nicola Ternette
contact affiliation	University of Oxford
contact email	nicola.ternette@ndm.ox.ac.uk
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/2019/11/PXD015489

PRIDE project URI

• PRIDE
  1. PXD015489
     1. Label: PRIDE project
     2. Name: Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection