Protein success could bring organ transplant hope

Monash University scientists, working in collaboration with Melbourne University, have solved the structure of an immune system protein that is crucial in keeping Epstein Barr Virus (EBV) infections in check, a development that could also improve the success of organ transplantation.

About 90% of the population is infected with EBV and the researchers have used X-ray crystallography to reveal the three-dimensional shape of the protein receptor, called a T-cell receptor, that stops EBV from wreaking havoc in the body.

They have used the same technique to solve the structure of a molecule called HLA B8 which transports EBV to the surface of cells where the virus is recognised and suppressed by the T-cell receptor.

Dr Jamie Rossjohn from Monash University said the findings gave great insight into the function of T-cell receptors in the body and might also lead to products that could reduce the rates of organ transplant rejection.

"The T-cell receptor we have studied interacts with Epstein Barr Virus and stops it from running rampant through the body but, in some transplant patients, the receptor can also interact with molecules in the organ being transplanted and contribute to it being rejected," Dr Rossjohn said.

Before organ transplant, patients are HLA typed (a process similar to blood typing) to check that the donor and the recipient are immunologically compatible.

About 25% of the Caucasian population is HLA type B44. There are several variants of HLA B44 and some of these can cause problems for organ recipients who are HLA type B8.

In the case of EBV infection, T-cell receptors bind to HLA B8 to stop the infection taking hold. But when a HLA B44 organ is donated to a HLA B8 patient the T-cell receptor sometimes interacts with the B44 molecules and causes transplant rejection.

"Now that we know the structure of the T-cell receptor we can also begin to understand the molecular basis for transplant rejection," Dr Rossjohn said. "If we can find a general mechanism for immune recognition of foreign tissues then perhaps this can be blocked so that transplants can proceed without fear of rejection," Dr Rossjohn said.

Item provided courtesy of Monash University