PXD069096

PXD069096 is an original dataset announced via ProteomeXchange.

Title	FVIII peptides presented on HLA-DP and identification of an A3 domain peptide binding with high affinity to the commonly expressed HLA-DP4
Description	The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) poses a major challenge in hemophilia A (HA) treatment. The formation of FVIII inhibitors is a CD4+ T-cell-dependent mechanism which includes anti- gen presenting cells (APC), B- and T-helper lymphocytes. APC present FVIII-derived peptides on major histocompatibility complex class II (MHC-II) to CD4+ T cells. We previously established a mass spectrometry-based approach to delineate the FVIII repertoire presented on HLA-DR and HLA-DQ. In this study, specific attention was directed towards the identification of FVIII peptides presented on HLA-DP. A data-set of naturally processed FVIII peptides was generated by incubating human FVIII with immature monocyte-derived dendritic cells (moDC) from HLA-typed healthy donors. Using this method, we iden- tified 176 to 1,352 different HLA-DP presented peptides per donor, including 26 different FVIII-derived peptides. The most frequently presented peptides derived from the A3 and C2 domains of FVIII. Comparison of the FVIII repertoire presented on HLA-DP with that presented on HLA-DR revealed considerable overlap but also suggested preferential presentation of specific peptides on either HLA-DR or HLA-DP. Fourteen FVIII peptides presented on HLA-DP were synthesized and evalu- ated for their binding ability to the commonly expressed HLA-DP4 molecule which is highly prevalent in the Caucasian population. Peptide binding studies showed that 7 of 14 peptides competed with a reference peptide to HLA-DP4. Interest- ingly, an A3 domain-derived peptide bound with high affinity to HLA-DP4, positioning this peptide as a prime candidate for the development of novel peptide-based tolerogenic strategies for FVIII inhibitors.
HostingRepository	PRIDE
AnnounceDate	2025-10-03
AnnouncementXML	Submission_2025-10-03_01:17:27.373.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arie Hoogendijk
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-02 14:02:40	ID requested
⏵ 1	2025-10-03 01:17:28	announced

10.3324/haematol.2024.286204;

Miranda M, Hansen BE, Wehbi B, Porcheddu V, Van Alphen FPJ, Kaijen P, Fijnvandraat K, Lacroix-Desmazes S, Van den Biggelaar M, Maillere B, Voorberg J, Consortium E, FVIII peptides presented on HLA-DP and identification of an A3 domain peptide binding with high affinity to the commonly expressed HLA-DP4. Haematologica, 110(6):1316-1327(2025) [pubmed]

submitter keyword: hemophilia A, inhibitors, immunity,factor VIII

A.J. Hoogendijk
contact affiliation	Sanquin Research, Amsterdam, NL
contact email	a.hoogendijk@sanquin.nl
lab head
Arie Hoogendijk
contact affiliation	Sanquin Research, Amsterdam
contact email	a.hoogendijk@sanquin.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069096
     1. Label: PRIDE project
     2. Name: FVIII peptides presented on HLA-DP and identification of an A3 domain peptide binding with high affinity to the commonly expressed HLA-DP4