PXD024109

PXD024109 is an original dataset announced via ProteomeXchange.

Title	ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29
Description	Birdshot Uveitis (BU) is a blinding inflammatory eye condition that only affects HLA-A29-positive individuals. Genetic association studies linked ERAP2 with BU, an aminopeptidase which trims peptides before their presentation by HLA class I at the cell surface, which suggests that ERAP2-dependent peptide presentation by HLA-A29 drives the pathogenesis of BU. However, it remains poorly understood whether the effects of ERAP2 on the HLA-A29 peptidome are distinct from its effect on other HLA allotypes. To address this, we focused on the effects of ERAP2 on the immunopeptidome in patientderived antigen presenting cells. Using complementary HLA-A29-based and pan-class I immunopurifications, isotope-labeled naturally processed and presented HLA-bound peptides were sequenced by mass spectrometry. We show that the effects of ERAP2 on the N-terminus of ligands of HLA-A29 are shared across endogenous HLA allotypes, but discover and replicate that one peptide motif generated in the presence of ERAP2 is specifically bound by HLA-A29. This motif can be found in the amino acid sequence of putative autoantigens. We further show evidence for internal sequence specificity for ERAP2 imprinted in the immunopeptidome. These results reveal that ERAP2 can generate an HLA-A29-specific antigen repertoire, which supports that antigen presentation is a key disease pathway in BU.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_15:16:01.184.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	W.J. Venema
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-10 05:38:52	ID requested
⏵ 1	2022-02-16 15:16:02	announced

Venema WJ, Hiddingh S, de Boer JH, Claas FHJ, Mulder A, den Hollander AI, Stratikos E, Sarkizova S, van der Veken LT, Janssen GMC, van Veelen PA, Kuiper JJW, ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29. Front Immunol, 12():634441(2021) [pubmed]

submitter keyword: Birdshot, HLA-A29, ERAP2, autoimmunity, immunopeptidome

Jonas J.W. Kuiper
contact affiliation	Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands. Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands.
contact email	j.j.w.kuiper@umcutrecht.nl
lab head
W.J. Venema
contact affiliation	Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
contact email	w.j.venema@umcutrecht.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024109
     1. Label: PRIDE project
     2. Name: ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29