What are antigens/epitopes are recognized in by islet-infiltrating CD8+ T cells in people with type 1 diabetes?

Research Opportunity
PhD, Master of Biomedical Science
Number of Master Places Available
1
Department
Medicine and Radiology
Location
St Vincent's Institute of Medical Research
Primary Supervisor Email Number Webpage
A/Prof Stuart Mannering smannering@svi.edu.au Personal web page
Co-supervisor Email Number Webpage
Dr Colleen Elso celso@svi.edu.au
Prof Helen Thomas hthomas@svi.edu.au

Summary This project will reveal the epitopes seen by human CD8+ T cells strongly implicated in the immune pathogenesis of type 1 diabetes. The student will learn state-of-the-art human T-cell immunology, retroviral transduction and molecular biology techniques in a stimulating and supportive environment.

Project Details

Type 1 diabetes is an autoimmune disease caused by the combined actions of CD4+ and CD8+ T-cell against the insulin-secreting beta cells found in the islets of Langerhans in the pancreas. While CD4+ T cells are the principal regulators of the (auto)immune response, CD8+ T cells are believed to be the primary ‘killers’ of beta cells in type 1 diabetes.  However, the antigens/epitopes that are ‘seen’ by pathogenic CD8+ T cells are not defined. This is an important question because knowledge of the targets of CD8+ T cells is essential for the development of new therapies to prevent type 1 diabetes. In addition, this is a major gap in our understanding of human autoimmunity in type 1 diabetes.

We pioneered techniques for isolating and characterising human islet-infiltrating T cells (Pathiraja et al. Diabetes 2015), We now have a large panel of CD8+ T cells, or TCR sequences, from the residual pancreatic islet of seven deceased organ donors who suffered from T1D. This gives us a unique panel of CD8+ T-cell clones strongly implicated in the pathogenesis of human T1D to study.

We have established techniques for screening large of human TCRs for responses to numbers of beta cell antigens. This project will reveal the epitopes seen by human CD8+ T cells strongly implicated in the immune pathogenesis of type 1 diabetes. The student will learn state-of-the-art human T-cell immunology, retroviral transduction and molecular biology techniques in a stimulating and supportive environment.



Faculty Research Themes

Infection and Immunology

School Research Themes

Cardiometabolic



Research Opportunities

PhD, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

St Vincent's Institute of Medical Research

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