June 25, 2009

Infiltration of T cells into the brain and spinal cord is part of the immune response seen in MS. Once in the central nervous system, T cells emit molecules that perform functions such as signaling other cells. First, however, T cells must be activated. Activation happens when the T-cell receptor (a molecule extending from the surface of the T cell) successfully binds to a protein fragment that is also bound to an HLA molecule extending from the surface of another cell. The HLA molecules and T-cell receptors that are expressed by a person's cells bind only to specific protein fragments; therefore learning what these particular fragments are in people with MS could help us better understand the disease. Previous research has given some idea of the central nervous system proteins that might be involved in the MS immune response, but technology has now evolved to the point of being able to show the exact fragments that T cells might "see" in the MS brain.

A team of researchers, using autopsy brain samples from 8 people with MS, were able to separate out the HLA molecules in the tissue and were then able to determine which segments of which proteins those HLA molecules were binding. They identified 174 proteins all together. Not surprisingly, most of the MS subjects had HLA molecules that bound a fragment of MBP (myelin basic protein), which is an abundant protein in myelin and a known target of T cells. Other fragments identified belonged to proteins that are involved in remyelination, neurodegeneration, cell death (apoptosis), astrocyte scarring, cell signaling, etc. Further analysis of the results of this study (and similar studies that may be published in the future) could lead to a better understanding of the immune response in MS and perhaps even targeted therapies that block the immune reaction to specific proteins.

This study is interesting because it reveals a new aspect of the actual state of affairs in MS. Unfortunately, it requires actual brain tissue samples and so its applicability will be limited to autopsy cases and rare biopsy tissue samples.