Integral use of immunopeptidomics and immunoinformatics for the characterization of antigen presentation and rational identification of BoLA-DR-presented peptides and epitopes

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  • Andressa Fisch
  • Birkir Reynisson
  • Lindert Benedictus
  • Annalisa Nicastri
  • Deepali Vasoya
  • Ivan Morrison
  • Buus, Søren
  • Beatriz Rossetti Ferreira
  • Isabel Kinney Ferreira De Miranda Santos
  • Nicola Ternette
  • Tim Connelley
  • Morten Nielsen

MHC peptide binding and presentation is the most selective event defining the landscape of T cell epitopes. Consequently, understanding the diversity of MHC alleles in a given population and the parameters that define the set of ligands that can be bound and presented by each of these alleles (the immunopeptidome) has an enormous impact on our capacity to predict and manipulate the potential of protein Ags to elicit functional T cell responses. Liquid chromatography-mass spectrometry analysis of MHC-eluted ligand data has proven to be a powerful technique for identifying such peptidomes, and methods integrating such data for prediction of Ag presentation have reached a high level of accuracy for both MHC class I and class II. In this study, we demonstrate how these techniques and prediction methods can be readily extended to the bovine leukocyte Ag class II DR locus (BoLA-DR). BoLA-DR binding motifs were characterized by eluted ligand data derived from bovine cell lines expressing a range of DRB3 alleles prevalent in Holstein-Friesian populations. The model generated (NetBoLAIIpan, available as a Web server at NetBoLAIIpan) was shown to have unprecedented predictive power to identify known BoLA-DR-restricted CD4 epitopes. In summary, the results demonstrate the power of an integrated approach combining advanced mass spectrometry peptidomics with immunoinformatics for characterization of the BoLA-DR Ag presentation system and provide a prediction tool that can be used to assist in rational evaluation and selection of bovine CD4 T cell epitopes.

TidsskriftJournal of Immunology
Udgave nummer10
Sider (fra-til)2489-2497
Antal sider9
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Agreement OPP1127286) under the auspices of the Centre for Tropical Livestock Genetics and Health, established jointly by the University of Edinburgh, Scotland’s Rural College, and the International Livestock Research Institute; and the Biotechnology and Biological Sciences Research Council through an Institute Strategic Programme award made to The Roslin Institute (BBS/E/D/20002174). The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill and Melinda Gates Foundation nor the U.K. Government.

Funding Information:
This work was supported in part by funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract HHSN272201200010C; the Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2015/09683-9 to B.R.F., Scholarships 2014/11010-9, 2017/21401-4, and 2018/23579-8 to A.F.); the Bill and Melinda Gates Foundation with U.K. aid from the U.K Foreign, Commonwealth, and Development Office (Grant

Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.

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