Improved Prediction of Bovine Leucocyte Antigens (BoLA) Presented Ligands by Use of Mass-Spectrometry-Determined Ligand and in Vitro Binding Data

Morten Nielsen*, Tim Connelley, Nicola Ternette

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

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    Abstract

    Peptide binding to MHC class I molecules is the single most selective step in antigen presentation and the strongest single correlate to peptide cellular immunogenicity. The cost of experimentally characterizing the rules of peptide presentation for a given MHC-I molecule is extensive, and predictors of peptide-MHC interactions constitute an attractive alternative. Recently, an increasing amount of MHC presented peptides identified by mass spectrometry (MS ligands) has been published. Handling and interpretation of MS ligand data is, in general, challenging due to the polyspecificity nature of the data. We here outline a general pipeline for dealing with this challenge and accurately annotate ligands to the relevant MHC-I molecule they were eluted from by use of GibbsClustering and binding motif information inferred from in silico models. We illustrate the approach here in the context of MHC-I molecules (BoLA) of cattle. Next, we demonstrate how such annotated BoLA MS ligand data can readily be integrated with in vitro binding affinity data in a prediction model with very high and unprecedented performance for identification of BoLA-I restricted T-cell epitopes. The prediction model is freely available at http://www.cbs.dtu.dk/services/NetMHCpan/NetBoLApan . The approach has here been applied to the BoLA-I system, but the pipeline is readily applicable to MHC systems in other species.
    Original languageEnglish
    JournalJournal of Proteome Research
    Volume17
    Issue number1
    Pages (from-to)559-567
    ISSN1535-3893
    DOIs
    Publication statusPublished - 2018

    Keywords

    • BoLA
    • GibbsClustering
    • MHC
    • NetMHCpan
    • T-cell epitopes
    • Antigen presentation
    • Bioinformatics
    • Mass spectrometry
    • Prediction

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