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Do the T cells that cause type 1 diabetes in humans recognize hybrid peptides?

Do the T cells that cause type 1 diabetes in humans recognize hybrid peptides?

PhD/Honours project

Autoimmune diseases have been a puzzle for immunologist for many years. The central question is: why does the immune system turn against healthy tissue? One hypothesis that has gather experimental support is that the immune system responds to self proteins that have been changed. These are termed posttranslational modifications. The problem is that almost every protein can be modified and many proteins must be altered to perform their function in the cell. The challenge is to identify the changes that create new targets for the autoimmune response. Recently we, with our collaborators in the USA, made a breakthrough. We found that the targets of human autoimmune T-cell responses in type 1 diabetes recognize short pieces of protein, call peptides, which are made by the fusion of peptides from two different proteins. Because insulin is one half of these hybrids we’ve called these peptides Hybrid Insulin Peptides, or HIPs (Delong et al. Science, 2016). The aim of this project is to look for new HIPs that stimulate human CD4+ T cells isolated from the pancreatic islets of deceased organ donors who had type 1 diabetes (Pathiraja et al. Diabetes 2015).  This will be done by testing CD4+ T cells for responses, measured by IFNg ELISA, to synthetic peptides that mimic the sequence of putative HIPs. Further experiments will validate responses to these HIPs in peripheral blood mononuclear cells (PBMC) from people with and without type 1 diabetes. An analysis of the HIP’s binding affinity to HLA class II and their presence in human beta cells will also be investigated.

This project is an opportunity to gain expertize in human T-cell immunology in a very new field. The student working on this project will gain experience in cellular immunology, flow cytometry, tissue culture, peptide chemistry and mass spectrometry.

Supervised by:

  • A/Prof Stuart Mannering
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Human T cell