Research: EBV and T cell responses

EpubJilek et al. HLA-B7-Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis.J Immunol. 2012 Mar 28.

Another bit of highbrow immunology.

It is hypothesised that the EBV-specific CD8(+) T cell response may be dysregulated in MSers, possibly leading to a suboptimal control of this virus. 

"CD8+ T-cells are white blood cells that attack virus infected cells."

To examine the CD8(+) T cell response in greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and Cytomegalovirus (CMV)-specific CD8(+) T cell responses in MSers and control subjects. 

"Remember that HLA molecules are the message board that cells use to communicate with the immune system. If the messages or proteins they stick in  these HLA molecules come from viruses then the immune cells attack an kill these cells."

"Cytomegalovirus of CMV is a human herpes virus related to EBV. Investigators then to study to virus in parallel to EBV as a control virus. All good scientific experiments include controls."

The researchers findings suggest that the HLA-B*0702-restricted viral (in particular the EBV)-specific CD8(+) T cell response is dysregulated in MSers. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MSers. This is  interesting considering that EBV infection is so strongly associated with MS.


"The Human Leucocyte antigen (HLA) is the place in the human genome that is used for DNA fingerprinting because it is variable betweeen people and is used by the immune system to detect invaders (bacteria, virus etc.). For each person they have one set of of A molecules, one set of B molecules and one set of C molecules from each parent. The HLA-A,B,C molecules are designed to help detect invaders within cells such that they are then killed by cytotoxic (cell killing) T cells called CD8 cells. These would recognise the invader in combination with the HLA-A, HLA-B or HLA-C molecules and then punch holes in the infected cell to kill it. There are another set of molecules called HLA-D (DR, DQ and DQ) that are recognised by CD4 cells and this system is designed to find invaders outside of a cell. In MS there appears to be a preponderence of CD8 T cells in the brain of MSers sugggesting that their may be a virus there. Cytomegalovirus is a common virus in humans as is used as a control. MSers had more of a variant of the HLA-B molcule than non-MSers. They then detected the number of cells specific for virus using a technology called tetramers a staining agent made up of four synthetic HLA-molecules containing an amino acid sequence from the virus of interest. These were less responsiveness in MS to EBV. Does this mean that rather than being in the blood the cells are in the brain, or could there be altered responses to another bit of the Epstein Barr Virus?"

"I assume most of you won't have clue about the immunology in this post; it is a complicated subject. This work tells us that there is something wrong with the immune system in MSers when it comes to controlling EBV."

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