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

Author(s):Show less -

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

• Document type: Journal article
• Source: VACCINES; v. 10, n. 11, p. 35-pg., 2022-11-01.

Abstract

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. (AU)

• FAPESP's process: 17/21401-4 - Seeking vaccine antigen epitopes presented by BoLA-DR for development of a multi epitope-based vaccine against R. microplus tick infestations
• Grantee: Andressa Fisch
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/23579-8 - Development of a recombinant multicomponent chimeric vaccine based in protein epitopes from Rhipicephalus microplus ticks
• Grantee: Andressa Fisch
• Support Opportunities: Scholarships in Brazil - Post-Doctoral