- Prof. James McCluskey, Principal Investigator
- Dr. Jamie Rossjohn, Co-Investigator
- Dr. Andrew Brooks, Co-Investigator
- Dr. Anthony Purcell, Associate
- University of Melbourne, Melbourne, Australia
- Defining the Molecular Basis of T Cell Allorecognition
Long-term transplant rejection in recipients of kidney and other solid organ transplants is due to an attack on the grafted organ by the T cells of the immune system. This attack results from mistaken identity of the transplanted tissue that resembles an infection to the unsuspecting immune system. The molecular recognition events that occur in transplant rejection are very poorly understood. This research aims to determine exactly how and why this case of mistaken identity occurs at a molecular level.
The project will first determine the three-dimensional structure of several protein receptors that T cells normally use to detect common viral infections but which are also known to attack tissue grafts from unrelated individuals. We will also identify the exact molecules that are recognised on transplanted organs during immune rejection and compare these with the molecules that are normally recognised during viral infections. Once these molecules are identified we plan to determine their shape at the atomic level by X-ray crystallography. By comparing exactly how the same receptors that recognise viruses also recognise foreign tissues we hope to learn more about the basic mechanisms by which T cell receptors interact with host tissues and organ grafts.
The molecular details by which host T cells recognise transplanted tissues may allow us to design ways of monitoring immunological rejection events in transplanted patients and perhaps permit us to design decoy molecules that could subvert the rejection process.