Immunopeptidomic Analysis of BoLA-I and BoLA-DR Presented Peptides from Theileria parva Infected Cells

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  • Timothy Connelley
  • Annalisa Nicastri
  • Tara Sheldrake
  • Christina Vrettou
  • Andressa Fisch
  • Birkir Reynisson
  • Buus, Søren
  • Adrian Hill
  • Ivan Morrison
  • Morten Nielsen
  • Nicola Ternette

The apicomplexan parasite Theileria parva is the causative agent of East Coast fever, usually a fatal disease for cattle, which is prevalent in large areas of eastern, central, and southern Africa. Protective immunity against T. parva is mediated by CD8+ T cells, with CD4+ T-cells thought to be important in facilitating the full maturation and development of the CD8+ T-cell response. T. parva has a large proteome, with >4000 protein-coding genes, making T-cell antigen identification using conventional screening approaches laborious and expensive. To date, only a limited number of T-cell antigens have been described. Novel approaches for identifying candidate antigens for T. parva are required to replace and/or complement those currently employed. In this study, we report on the use of immunopeptidomics to study the repertoire of T. parva peptides presented by both BoLA-I and BoLA-DR molecules on infected cells. The study reports on peptides identified from the analysis of 13 BoLA-I and 6 BoLA-DR datasets covering a range of different BoLA genotypes. This represents the most comprehensive immunopeptidomic dataset available for any eukaryotic pathogen to date. Examination of the immunopeptidome data suggested the presence of a large number of coprecipitated and non-MHC-binding peptides. As part of the work, a pipeline to curate the datasets to remove these peptides was developed and used to generate a final list of 74 BoLA-I and 15 BoLA-DR-presented peptides. Together, the data demonstrated the utility of immunopeptidomics as a method to identify novel T-cell antigens for T. parva and the importance of careful curation and the application of high-quality immunoinformatics to parse the data generated.

Udgave nummer11
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
This work was supported by funds from multiple sources, including DfiD and the Bill and Melinda Gates Foundation through the ‘Improved vaccines for the control of East Coast Fever in cattle in Africa’ grant (OPP1078791); the BBSRC through the ISP award made to the Roslin Institute (BBS/E/D/20002174); a small grant award from the Roslin Foundation; and a FAPESP scholarship awarded to AF (2014/11010-9, 2017/21401-4, and 2018/23579-8). The findings and conclusions contained within are those of the authors and do not necessarily reflect the positions or policies of the Bill and Melinda Gates Foundation, the UK Government, or any of the other funders.

Publisher Copyright:
© 2022 by the authors.

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