CD4 T cell responses to Theileria parva in immune cattle recognise a diverse set of parasite antigens presented on the surface of infected lymphoblasts

Ivan Morrison, Adriana Aguado-Martinez, Tara Sheldrake, Nicholas C Palmateer, Olukemi O Ifeonu, Kyle Tretina, Keith Parsons , Emilio Fenoy, Tim Connelley, Morten Nielsen, Joana C. Silva

Research output: Contribution to journalArticlepeer-review

Abstract

Parasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus) and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for antigen identification using CD4 T cells from immune animals to screen a library of ~40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells from 12 immune cattle, representing 12 class II MHC types, identified 26 antigens. Unlike CD8 T cell responses, which are focused on a few dominant antigens, multiple antigens were recognised by CD4 T cell responses of individual animals. The antigens had diverse properties, but included proteins encoded by two multi-member gene families – five haloacid dehalogenases and five subtelomere-encoded variable secreted proteins (SVSPs). Most antigens had predicted signal peptides and/or were encoded by abundantly transcribed genes, but neither parameter on their own was reliable for predicting antigenicity. Mapping of the epitopes confirmed presentation by DR or DQ class II alleles and comparison of available T. parva genome sequences demonstrated that they included both conserved and polymorphic epitopes. Immunisation of animals with vaccine vectors expressing two of the antigens demonstrated induction of CD4 T cell responses capable of recognising parasitised cells. The results of this study provide detailed insight into the CD4 T cell responses induced by T. parva, and identify antigens suitable for use in vaccine development.
Original languageEnglish
JournalJournal of Immunology
Early online date10 Sep 2021
DOIs
Publication statusE-pub ahead of print - 10 Sep 2021

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