Poster Presentation International Veterinary Immunology Symposium 2016

Analysis of MHCI presented peptides from T. parva by mass spectrometry to identify potential vaccine candidates (#144)

Nicola Ternette 1 , Morten Nielsen 2 , Soren Buus 3 , Niall MacHugh 4 , Ivan Morrison 4 , Timothy Connelley 4
  1. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
  2. Centre for Biological Sequence Analysis , The Technical University of Denmark, Copenhagen, Denmark
  3. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
  4. The Roslin Institute, Roslin, MIDLOTHIAN, United Kingdom

Vaccines that elicit protective T-cell responses are required against a range of human and veterinary pathogens. Subunit vaccines, which contain defined antigens, have demonstrated a capacity to generate T-cell responses in a variety of models. A pre-requisite for the development of such vaccines is the identification of relevant T-cell epitopes. Traditionally, antigen identification has been achieved by studying the epitope-specificity of T-cell populations from immunised individuals. However, for eukaryotic pathogens, such as Plasmodium and Theileria, the combination of host MHC diversity, large pathogen proteomes and strain variation makes identification of antigens that would be broadly protective in an outbred population a considerable obstacle to rational vaccine design. Identification of pathogen-derived peptides presented on infected cells would provide an alternative set of peptides that may serve as potential vaccine candidates. Recent developments in mass spectrometry and bioinformatics have opened up opportunities to use MHC elution as a technology to identify the repertoire of MHC presented epitopes. In a set of preliminary studies analysing T. parva-infected cells from 4 MHCI-homozygous animals we have identified peptides derived from 29 T. parva proteins. These include 3 antigens that contain defined CD8+ T-cell epitopes. Conventional epitope screening using a CD8+ T-cell lines from a range of MHC-defined animals will be conducted to evaluate the utility of this approach to refine antigen screening.