Furthermore, the capability to broadly characterize antibody repertoires at the epitope level could be used to identify conserved pathogen epitopes and tumor specific antigen epitopes to aid in therapeutic discovery.Ī disease with prominent antibody responses is the common viral infection HSV, which causes human infections in the orofacial region (“cold sores”) and the genital region (“genital ulcers”). A detailed record of immune exposures can also facilitate the identification of biomarkers to diagnose infectious, autoimmune, and allergic conditions. Such information has proven useful for correlating antibody responses with disease outcomes to design more effective vaccines. The ability to more fully interrogate immunological memory could reveal exposures to pathogens, commensal organisms, and allergens. This immunological information is archived within the genes encoding B-cell and T-cell receptors along with the corresponding receptor structures, but has proven difficult to characterize in a comprehensive manner. For example, the adaptive immune response to many vaccinations is often sustained throughout an individual’s lifetime. Immunological memory allows for rapid antibody responses towards diverse antigens long after initial exposure. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: PSD is a Director, Officer, and Stockholder, and TJ and JDB are Employees of immune repertoire mapping company SerImmune. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All 278 antibody-binding peptide files are available from the Dryad Digital Repository ( ).įunding: This work was funded in part by grant M2016219 from the Brightfocus Foundation ( ) to PSD. Received: Accepted: AugPublished: September 6, 2019Ĭopyright: © 2019 Paull et al. Cheshenko, Albert Einstein College of Medicine, UNITED STATES The K-TOPE approach thus provides a powerful new tool to elucidate the organisms, antigens, and epitopes targeted by human antibody repertoires.Ĭitation: Paull ML, Johnston T, Ibsen KN, Bozekowski JD, Daugherty PS (2019) A general approach for predicting protein epitopes targeted by antibody repertoires using whole proteomes. Experimentally validating these candidate epitopes could help identify diagnostic biomarkers, vaccine components, and therapeutic targets. Additionally, we predicted 30 HSV2-specific epitopes that were 100% specific against HSV1 in novel and previously reported antigens. Twelve of these common viral and bacterial epitopes agreed with previously mapped epitopes with p-values < 0.05. Analysis of Staphylococcus and Streptococcus proteomes similarly predicted 22 epitopes recognized by >30% of specimens. An analysis of 2,908 proteins from 400 viral taxa that infect humans predicted seven enterovirus epitopes and five Epstein-Barr virus epitopes recognized by >30% of specimens. K-TOPE characterized a commonly targeted antigen from Rhinovirus A, predicting four epitopes recognized by antibodies present in 87% of sera (n = 250). As a positive control, we used this approach, termed K-mer Tiling of Protein Epitopes (K-TOPE), to predict epitopes targeted by monoclonal and polyclonal antibodies of well-characterized specificity, accurately recovering their known epitopes. We used the enrichment over background of these k-mers in the antibody-binding peptide dataset to predict antibody-binding epitopes. To predict antibody-binding epitopes and the antigens from which these epitopes were derived, we tiled the sequences of candidate antigens into short overlapping subsequences of length k (k-mers). Specifically, we selected antibody-binding peptides for 273 distinct sera out of a random library and identified the peptides using next-generation sequencing. To aid in characterization, we developed a generalizable strategy to predict antibody-binding epitopes within individual proteins and entire proteomes. Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized.
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