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Despite the potential for MS lesions to occur anywhere throughout the brain and spinal cord, many people with MS develop lesions that have a more restricted distribution. Dr Greer and colleagues have shown recently that, in a subgroup of people who develop MS affecting areas of the brain that control balance and coordination, a molecule that makes up myelin known as proteolipid protein (PLP) is a major target of the autoimmune attack.
The long-term aim of this work is to specifically stop the attack on PLP; however, in order to do this, a better idea of exactly how the immune system attacks PLP and why this leads to development of lesions in a fairly restricted area of the brain is necessary. This research project will investigate these issues.
Dr Greer and colleagues have been investigating the exact mechanism of attack on PLP by the immune system. Dr Greer’s research is focusing on small fragments of the protein called peptides and their interaction with the Major Histocompatibility Complex (MHC) and HLA molecules which play a central role in immunity. Using a range of experiments, Dr Greer is attempting to identify the minimum length of peptide that can be presented by the HLA molecules in order to invoke an immune response. In a laboratory system, she has tested and found certain PLP protein fragments bind more strongly than others, depending on the version of the MHC. She found that the DQ8 MHC subtype seems to be able to interact very strongly. The DQ8 subtype is the one which confers susceptibility to Type 1 Diabetes.
Dr Greer has also confirmed some of these findings in cells taken from people with MS that have been grown in the laboratory and is in the process of determining the immune cell response to PLP. While the work is still ongoing, there appears to be a signalling molecule signature that defines the immune cell response in these cases.
Finally, Dr Greer ran experiments to determine the important parts of the PLP peptide for the immune response. She found that one end of the peptide, the N-terminal, seemed to be the most important for the interaction with the immune molecules. Reactivity to PLP in this region also seemed to be related to the individual’s likelihood of developing lesions that affect balance and coordination, extending her previous work.
It is hoped that this important research will lead to new treatments that will specifically stop the autoimmune attack on PLP and thus prevent demyelination.
Updated: 12 June 2013
Dr Judith Greer
Professor Michael Pender
$270,000
2010
3 years
Past project
