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EASTBIO Functional studies of T cell-mediated immunity in birds


Project Description

Royal (Dick) School of Veterinary Studies / The Roslin Institute

T cell-mediated immunity in birds, as in mammals, requires antigen uptake and presentation via antigen-presenting cells (APCs) suggesting that modulation of APC function is a rational target for optimising vaccine efficiency in birds. In jawed vertebrates a central element of T cell-mediated adaptive immune responses is the clonal expansion of antigen-specific T cells from a large pool of cells bearing a broad repertoire of unique receptors T cell receptors (TCR). Mechanistically this is achieved by TCR recognition of cognate T cell epitopes presented on the surface of APC, which results in the activation, proliferation and differentiation of T cells. The T cell epitope consist of the combination of antigenic peptide bound to major histocompatibility complex (MHC) class I or II molecule. While it is relatively straightforward to measure the relative abundance of cells with specific TCRs after antigen exposure, the prediction of which specific TCR recognises a particular T cell epitope remains elusive in all animal and human models.

To date no chicken TCR that recognises a specific MHC class II–peptide partner has been identified. This severely limits the study of T cell-mediated immunity in birds, including the initiation and regulation of the immune response by APCs. The study of T cells responses after pathogen challenge or vaccination of chickens is further confounded by the lack of appropriate assays to identify and functionally characterise antigen-specific T-cell responses. Consequently the dynamics of antigen specific CD4+ T cell activation, expansion and function after pathogen challenge or vaccination in chickens is poorly defined. One effective method for the identification of T cells bearing TCR that recognise a specific MHC class II-peptide is the use of labelled soluble MHC-peptide ligands. In mammalian studies these MHC class II “tetramers” have proved to be an invaluable tool for characterisation of antigen specific CD4+ T cell responses. The Kaufman group has identified a number of different chicken MHC class II molecules with defined pathogen peptides which can now be used to produce chicken MHC class II tetramers.

This project will use cutting edge technologies (novel gene edited chicken lines, single cell sequencing, MHC class II/peptide tetramers) to eliminate this roadblock in avian immunological studies by:
• Generating defined pathogen peptide-MHC class II tetramers
• Using MHC class II tetramers to characterise the phenotype, location and function of antigen specific CD4+ T cells during pathogen challenge or vaccination.
• determine the gene sequences that express TCR molecules recognising particular peptide-MHC tetramers.
• Using single cell sequencing transcriptomics to identifies distinct CD4+ T cell subpopulations during pathogen challenge or vaccination.
• Developing in vitro assays, such as cell proliferation and cytokine secretion, to functionally characterise CD4+ T cell responses.
• Using novel gene edited and transgenic chicken lines to determine the contribution of specific APC subsets to the development of CD4+ T cell responses.

At completion of this project, we will have a better understanding of the dynamics of antigen specific CD4+ T cell responses in the chicken which can inform future vaccination and selective breeding approaches.


Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.

Funding Notes

Applications:
Completed application form along with your supporting documents should be sent to our PGR student team at

References:
Please send the reference request form to two referees. Completed forms for University of Edinburgh, Royal (Dick) School of Veterinary Studies and the Roslin Institute project should be returned to by the closing date: 5th January 2020.

It is your responsibility to ensure that references are provided by the specified deadline.
Download application and reference forms via:
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