CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts

Abstract

Parasite-specific CD8 T cell responses play a key role in mediating immunity againstTheileria 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. Key points  Multiple CD4 T cell antigens identified by screening a T. parva peptide library  Antigens have diverse properties and include polymorphic and conserved proteins  Parasite infection and viral-vector delivered antigen induce similar CD4 responses

Systematic Determination of TCR–Antigen and Peptide–MHC Binding Kinetics among Field Variants of a Theileria parva Polymorphic CTL Epitope

“…Because we did not have these strains isolated and produced as stabilates for immunization, this was not possible to investigate. However, this Ag may still be used as a promising cellular immune Ag because it induces CD4 + T cell responses in several MHC class II haplotype backgrounds ( 49 , 52 ). Alternatively, several identified T. parva CTL Ags, such as Tp5, which are not polymorphic or show very little polymorphism, could be combined with Tp9 to induce broad CD4 + and CD8 + protective T cell responses.…”

Comparative transcriptional analysis identifies genes associated with the attenuation of Theileria parva infected cells after long-term in vitro culture

“…Most of the characterised T. parva antigens (including Tp1-10, Tp12-36, p32 and p67) [64][65][66] were nondifferentially expressed at day 7 and day 69the only exceptions were Tp3 (TpMuguga_01g00868) and p32 (TpMuguga_01g01056), which were both upregulated at day 69 (Figure 7a and b, and Supplementary File 6). The upregulation of p32, which is a merozoite surface antigen 67 , at day 69 fits in with the biological life-cycle of the parasite (i.e.…”

East Coast fever, a neglected tropical disease with an outdated vaccine approach?

“…Although Taracha and colleagues identified how antigen-specific CD4 + T cells promote CTL function in the Theileria model, CD4 + T cell antigens have not been specifically included in vaccines that were evaluated to date [15]. Morrison and colleagues have recently provided the first description of T. parva proteins with CD4 + T cell epitopes, which should feed into the antigen composition of future vaccines [10]. Similarly, γδ T cells recognise and lyse T. parva-infected cells [11], yet their role in T. parva immunity is unclear.…”