PXD043144

PXD043144 is an original dataset announced via ProteomeXchange.

Title	Human polyclonal anti-HLA LC-MS/MS
Description	Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) proteins mismatched between kidney transplant donors and recipients cause allograft loss. Using single cell, molecular, structural, and proteomic techniques, we profiled the HLA-specific (alloreactive) B cell response in kidney and blood of a transplant recipient with antibody-mediated rejection (AMR). We identified 14 distinct alloreactive B cell lineages, which spanned the rejected organ and blood and expressed high-affinity anti-donor HLA-specific B cell receptors – many of which were clonally linked to circulating DSA. The alloreactive B cell response was focused on exposed, solvent-accessible mismatched HLA residues, while also demonstrating extensive contacts with self-HLA residues. Consistent with structural evidence of self-recognition, measurable autoreactivity by donor-specific B cells was common and positively correlated with anti-donor affinity maturation. Thus, allo- and self-reactive signatures appeared to converge, suggesting that during AMR, the recognition of non-self and breaches of tolerance conspire to produce a pathogenic donor-specific adaptive response.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-07_16:07:03.776.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043144
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rodney King
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-20 13:55:08	ID requested
⏵ 1	2025-12-07 16:07:04	announced

10.1016/j.immuni.2025.10.014;

10.6019/PXD043144;

Killian JT, King RG, Lucander ACK, Kizziah JL, Fucile CF, Diaz-Avalos R, Qiu S, Silva-Sanchez A, Mousseau BJ, Macon KJ, Callahan AR, Yang G, Hossain ME, Akther J, Good DB, Kelso S, Houp JA, Rosenblum F, Porrett PM, Ong SC, Kumar V, Saphire EO, Kearney JF, Randall TD, Rosenberg AF, Green TJ, Lund FE, Topography of the HLA-A protein enforces shared and convergent immunodominant B cell and antibody alloresponses in transplant recipients. Immunity, 58(12):3040-3060.e12(2025) [pubmed]

submitter keyword: Human, antibody, HLA

R. Glenn King
contact affiliation	University of Alabama at Birmingham
contact email	rgking@uab.edu
lab head
Rodney King
contact affiliation	University of Alabama at Birmingham
contact email	rgking@uab.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043144
     1. Label: PRIDE project
     2. Name: Human polyclonal anti-HLA LC-MS/MS