Dataset Information

Germline encoded residues dominate the interaction of a human monoclonal antibody with Decorin binding protein A (DbpA) of Borrelia burgdorferi

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

DISEASE(S): Lyme Disease

SUBMITTER: Clint Vorauer

LAB HEAD: Miklos Guttman

PROVIDER: PXD062826 | Pride | 2025-07-28

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	DbpA.txt	Txt
	DbpAF945_ForPRIDE.7z	Other
	DbpA_coverage_nepII_1.csv	Csv

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Publications

Germline encoded residues dominate the interaction of a human monoclonal antibody with decorin binding protein A of Borrelia burgdorferi.

Rudolph Michael J MJ Muriuki Beatrice M BM Chen Yang Y Vance David J DJ Vorauer Clint C Piazza Carol Lyn CL Freeman-Gallant Grace G Golonka Rachel M RM Mirabile Gianna G Guttman Miklos M Cavacini Lisa A LA Mantis Nicholas J NJ

Frontiers in immunology 20250707

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. ...[more]

PMID: 40692775

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Project description:Epitope mapping studies aim to identify the binding sites of antibody-antigen interactions to enhance the development of vaccines, diagnostics and immunotherapeutic compounds. However, mapping is a laborious process employing time- and resource-consuming M-bM-^@M-^Xwet benchM-bM-^@M-^Y techniques or epitope prediction software that are still in their infancy. For polymorphic antigens, another challenge is characterizing cross-reactivity between epitopes, teasing out distinctions between broadly cross-reactive responses, limited cross-reactions among variants and the truly type-specific responses. A refined understanding of cross-reactive antibody binding could guide the selection of the most informative subsets of variants for diagnostics and multivalent subunit vaccines. We explored the antibody binding reactivity of sera from human patients and Peromyscus leucopus rodents infected with Borrelia burgdorferi to the polymorphic outer surface protein C (OspC), an attractive candidate antigen for vaccine and improved diagnostics for Lyme disease. We constructed a protein microarray displaying 23 natural variants of OspC and quantified the degree of cross-reactive antibody binding between all pairs of variants, using Pearson correlation calculated on the reactivity values using three independent transforms of the raw data: (1) logarithmic, (2) rank, and (3) binary indicators. We observed that the global amino acid sequence identity between OspC pairs was a poor predictor of cross-reactive antibody binding. Then we asked if specific regions of the protein would better explain the observed cross-reactive binding and performed in silico screening of the linear sequence and 3-dimensional structure of OspC. This analysis pointed to the C-terminal helix of the structure as a major determinant of type-specific cross-reactive antibody binding. We developed bioinformatics methods to systematically analyze the relationship between local sequence/structure variation and cross-reactive antibody binding patterns among variants of a polymorphic antigen, and this method can be applied to other polymorphic antigens for which immune response data is available for multiple variants. Antibody profiling was performed on sera from Borrelia burgdorferi infected and non-infected humans and Peromyscus leucopus rodents against 23 variants of the surface protein OspC . For infected human serum samples, the OspC type of the infecting B. burgdorferi strain is unknown; for experimentally-infected P. leucopus serum samples, it is known. Of human serum samples, 55 were from infected individuals and 25 from naive controls. Of P. leucopus serum samples, 23 were from infected individuals and 7 were from naive controls.

Dataset Information

Germline encoded residues dominate the interaction of a human monoclonal antibody with Decorin binding protein A (DbpA) of Borrelia burgdorferi

Dataset's files

Publications

Germline encoded residues dominate the interaction of a human monoclonal antibody with decorin binding protein A of <i>Borrelia burgdorferi</i>.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Germline encoded residues dominate the interaction of a human monoclonal antibody with Decorin binding protein A (DbpA) of Borrelia burgdorferi

Dataset's files

Publications

Germline encoded residues dominate the interaction of a human monoclonal antibody with decorin binding protein A of &lt;i&gt;Borrelia burgdorferi&lt;/i&gt;.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Germline encoded residues dominate the interaction of a human monoclonal antibody with decorin binding protein A of <i>Borrelia burgdorferi</i>.