MHC structure and the effect of heterozygosity in the immunodominance of bovine CD8+ T-cell responses against Theileria parva

CD8 T-cell responses are critical in conferring protective immunity against intra-cellular pathogens. CD8 T-cells recognise infected cells through epitopes presented by the polygenic and highly polymorphic MHCI molecules. Many CD8 T-cell responses exhibit immunodominance (focusing of an immune response on a limited number of epitopes) which has obvious implications for translational fields such as vaccine design. However, studies focusing on how MHC heterozygosity may influence immunodominance have been limited. In contrast to the murine and human MHCI systems, the cattle MHCI is characterised by variation in the number of MHCI genes expressed in different haplotypes and therefore offers extra dimensions in exploring how MHCI diversity influences immunodominance. We have (unpublished) evidence that in T. parva MHC heterozygosity can have profound effects on in the epitopes recognised by responding CD8 T-cell populations.

We are currently defining the Langhill herd MHC repertoire to provide a unique resource for studying MHCI diversity. Calves of a range of different MHCI haplotype combinations will be immunised against T. parva and in vitro analysis will be used to establish how epitope selection is influenced by heterozygosity and to determine if there is a hierarchy in MHCI alleles that dominate the subsequent immune response. The work has potential for expansion in a number of ways (e.g. if hierarchies exist is this consistent in responses to other pathogens? can knowledge of MHCI hierarchy be used to enable vaccines to circumvent immunodominance and allow broad immune responses to be generated?) which the student will play a role in determining and taking forward.

The group currently includes two PDRA and a bioinformatician. The student will have opportunities to receive training in a range of techniques, especially in ex vivo, in vitro immunology and bioinformatics with flexibility to also participate in in vivo work.

Application procedures
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

All applicants should also apply through the University’s on-line application system for September 2018 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=831

Applicants for the Principal’s career development studentship must also complete the specific on-line application form.

Applicants for an Enlightenment Scholarship must also complete the specific on-line application form.
ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 16th January 2018