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Understanding the relationship between myelin and immune system activation

A team of international researchers, including eminent Australian researcher Professor Claude Bernard from Monash University, has recently identified the specific sections of a myelin protein, known as myelin oligodendrocyte glycoprotein (MOG), that strongly activate the production of immune T cells in both humans and mice.

Earlier studies have identified that certain sections of the MOG protein may play an important role in causing immune system activation in MS and other demyelinating disorders. MOG is also commonly used to induce an MS-like illness in the animal model of MS known as experimental autoimmune encephalomyelitis (EAE). Published in the journal Neurology, Neuroimmunology and Neuroinflammation, these new findings help us to understand the mechanisms of how specific sections of the MOG protein may elicit an immune system reaction through the activation of T cells, and how this reaction may contribute to MS symptoms in mice and humans.

In two complementary articles published in the same journal, the researchers identified that within the MOG protein, there are certain sections of the protein that specifically trigger an antibody reaction. The researchers first isolated these sections and found that three key sections were able to strongly activate the production of self-reactive immune T cells in mice. In particular, one of these sections was found to be of key importance and was alone capable of inducing an EAE condition.

In the second article, the team showed that the immune systems of people with MS reacted much more strongly to the MOG protein compared to healthy individuals, producing significantly more activated T cells in response to the same three sections of the MOG protein and in particular a certain type of inflammatory cell known as Th17 cells, which are known play a key role in MS.

Understanding the mechanisms by which MOG can generate an immune response is vitally important for identifying and developing new treatments for MS. This work enables researchers to identify the most efficient sections of the MOG protein to target in order to have the greatest effect on the immune response to treat MS.

To this end, in a third paper was recently published in the Journal of Neuroimmunology, led by Professor Bernard. This work was supported by a MS Research Australia / Trish MS Research Foundation post-graduate scholarship awarded to Dr Natalie Payne, a researcher working with Professor Bernard. The team showed that a ‘vaccination’ with a modified version of one section of the MOG protein could protect mice from developing EAE, reduce the number of self-reactive T-cells in their blood, and reduce the immune system production of inflammatory chemicals. Even if given after EAE had already been induced, the MOG ‘vaccination’ was able to reduce the severity of disease.

While there is still much work to be done in this area, this is great progress towards the development of potential treatments for MS that build on this knowledge of how the MOG protein can interact with the immune system.

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Understanding the relationship between myelin and immune system activation