Careers & Students

How do HLA-DQ2 and DQ8 increase the risk of people developing type 1 diabetes?

How do HLA-DQ2 and DQ8 increase the risk of people developing type 1 diabetes?

PhD/Honours project

Type 1 diabetes is an autoimmune disease caused by the CD4+ and CD8+ T-cell response against the insulin-secreting beta cells found in the islets of Langerhans in the pancreas. Genome wide association studies (GWAS) have shown that HLA class II genes, HLA-DQ2 and DQ8 are the most strongly disposing to developing T1D of any genes.  The aim of this project is to investigate why HLA-DQ2 and DQ8 dramatically increase an individual’s risk of developing T1D. One hypothesis is that these HLA molecules are unstable until they bind particular peptides derived from pancreatic beta cells. Building on our recent work (Pathiraja et al. Diabetes 2015 & Delong et al. Science, 2016) this project will examine the impact of these peptides on the stability of T1D-associated HLA molecules.

This project will used retroviral mediated gene transfer of HLA genes into cell lines to investigate the stability of different HLA molecules (Miyadera et al. J. Clin. Invest. 2015). The capacity of cell lines expressing different combinations of HLA alleles will to present beta cell derived peptides to specific T cells will be examined. This project will give the student experience in human T-cell immunology, particularly in autoimmune diseases. A variety of laboratory techniques will be developed, including: retroviral production and transduction, flow cytometry, molecular cloning, T-cell cloning and analysis of T-cell function, ELISA.

Supervised by:

  • A/Prof Stuart Mannering
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Human T cell