PXD062826

PXD062826 is an original dataset announced via ProteomeXchange.

Title	Germline encoded residues dominate the interaction of a human monoclonal antibody with Decorin binding protein A (DbpA) of Borrelia burgdorferi
Description	During the course of Lyme disease, humans mount a robust and sustained antibody response against dozens of Borrelia burgdorferi outer surface lipoproteins. Identifying which antibodies are associated with spirochete clearance and disease resolution is of paramount importance in therapeutic development. In this study, we describe the isolation and structural characterization of a human monoclonal antibody (MAb) against decorin binding protein A (DbpA), one of the most immunogenic of B. burgdorferi’s outer surface proteins. High-resolution epitope mapping by HX-MS and X-ray crystallography revealed that F945 associates with a lateral face of DbpA in a side-on orientation without obstructing resides associated with DbpA’s ability to bind components of the extracellular matrix. The structure of the DbpA-F945 Fab complex revealed an outsized role for variable light chain (V L ) germline encoded residues in mediating DbpA interactions. In fact, the majority of the critical contacts between F945 and DbpA involved V k 1- 33 germline encoded residues, suggesting that certain human B cell receptors (BCR) may be preconfigured to recognize DbpA and therefore have a lower the threshold for B cell activation and clonal development. Passive administration of F945 IgG was not sufficient to protect against B. burgdorferi in a mouse model of needle infection, although a role for F945 in influencing B. burgdorferi tissue tropism or retention within specific niches cannot be ruled out. Collectively these results provide the first structural insight into human antibody response to DbpA with implications for understanding factors involved in disease resolution.
HostingRepository	PRIDE
AnnounceDate	2025-07-28
AnnouncementXML	Submission_2025-07-27_16:06:48.238.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Clint Vorauer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-10 17:30:55	ID requested
⏵ 1	2025-07-27 16:06:49	announced

10.3389/fimmu.2025.1611828;

Rudolph MJ, Muriuki BM, Chen Y, Vance DJ, Vorauer C, Piazza CL, Freeman-Gallant G, Golonka RM, Mirabile G, Guttman M, Cavacini LA, Mantis NJ, . Front Immunol, 16():1611828(2025) [pubmed]

ProteomeXchange project tag: Antibodies (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Monoclonal,Borrelia, DbpA, HDX-MS

Miklos Guttman
contact affiliation	Associate Professor, University of Washington
contact email	mguttman@uw.edu
lab head
Clint Vorauer
contact affiliation	University of Washington
contact email	vorauecr@uw.edu
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/2025/07/PXD062826

PRIDE project URI

• PRIDE
  1. PXD062826
     1. Label: PRIDE project
     2. Name: Germline encoded residues dominate the interaction of a human monoclonal antibody with Decorin binding protein A (DbpA) of Borrelia burgdorferi