PXD064980-1

PXD064980 is an original dataset announced via ProteomeXchange.

Title	A red blood cell-based antigen delivery system to facilitate T cell epitope presentation to induce peripheral tolerance to ADAMTS13 in immune-mediated TTP
Description	Aims Leveraging the tolerogenic nature of their natural clearance pathway, we aim to exploit red blood cells (RBCs) as an antigen delivery system to achieve persistent exposure to ADAMTS13-derived peptides, promoting antigen-specific attenuation of autoreactive CD4+ T cells and induction of regulatory T cells. Background Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially fatal autoimmune disease caused by a severe ADAMTS13 functional deficiency mediated by autoantibodies targeting ADAMTS13. Despite high survival rates achieved with current treatments, approximately 40% of patients experience relapses. Ensuring longer-lasting recovery by restoring immune tolerance towards ADAMTS13 remains a significant unmet need. Conclusion(s) Our strategy offers a modular and effective method for targeting antigenic peptides to RBCs for transfusion. Antigen-decorated RBCs are efficiently phagocytosed by macrophages and facilitate the presentation of FINVAPHAR on MHC II molecules, giving macrophages the ability to target ADAMTS13-specific T cells. Based on our results we propose that RBCs loaded with ADAMTS13-derived peptides containing immunodominant T cell epitopes represent a promising strategy for promoting tolerance in patients with iTTP. Methods A fusion peptide comprising the TAT cell-penetrating peptide and an immunodominant ADAMTS13-derived T cell epitope (FINVAPHAR core sequence) was designed. Binding of the fusion peptide to RBCs was monitored by flow cytometry and Imagestream. To examine whether this approach can facilitate antigen-presentation on MHC II molecules, peptide-loaded RBCs were fed to macrophages, followed by isolation of HLA-DR-peptide complexes to study the presented peptide repertoire via mass spectrometry. Results We found that the fusion peptide binds to RBCs in a concentration-dependent manner. Peptide-bound RBCs were efficiently phagocytosed by macrophages. Mass spectrometric analysis revealed that phagocytosis of peptide-loaded RBCs by macrophages results in the presentation of FINVAPHAR-containing sequences of varying lengths on MHCII molecules from HLA-DRB1*11 donors, confirming functional antigen presentation
HostingRepository	PRIDE
AnnounceDate	2025-07-25
AnnouncementXML	Submission_2025-07-25_04:46:16.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stijn Groten
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-13 01:27:51	ID requested
⏵ 1	2025-07-25 04:46:17	announced

Dataset with its publication pending

submitter keyword: ADAMTS13,iTTP, immunopeptidomics, antigen presentation

Prof. Jan Voorberg, PhD
contact affiliation	Sanquin Research, Amsterdam, the Netherlands
contact email	j.voorberg@sanquin.nl
lab head
Stijn Groten
contact affiliation	Sanquin Research
contact email	s.groten@sanquin.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064980
     1. Label: PRIDE project
     2. Name: A red blood cell-based antigen delivery system to facilitate T cell epitope presentation to induce peripheral tolerance to ADAMTS13 in immune-mediated TTP