An international study has found that immune cells of people with HLA-DR15 recognize certain microbes, such as the Epstein-Barr virus, very effectively. However, this “fitness” can lead to an undesired immune reaction against the person’s own brain tissue, according to a press release.

Approximately half of the people with multiple sclerosis (MS) have the HLA-DR15 gene variant, which is responsible for up to 60% of genetic risk. If carriers of the gene variant are infected with Epstein-Barr virus and have a symptomatic course of infection called Pfeiffer’s disease, the risk of MS increases 15-fold.

"There are therefore clear indications that the interaction between HLA-DR15 and infectious agents such as Epstein-Barr virus is significant for the development of the disease, even though the exact mechanisms behind this have not been understood until now,” said Dr Roland Martin, head of the Department of Neuroimmunology and MS Research at the University Hospital Zurich, in a press release.

The researchers first investigated which fragments that HLA-DR15 captured and presented to the immune cells, using 2 novel antibodies that recognize the 2 variants of HLA-DR15 that occur in MS patients with a very high level of specificity. The HLA-DR15 molecules in the thymus mainly present fragments of themselves, which was not previously known, according to the study.

The researchers also discovered how to recognize fragments of the Epstein-Barr virus if the carrier of the genetic variant becomes infected with it, since the fragments from the virus have a much stronger activating effect than the HLA-DR15 fragments. As a result, the T lymphocytes not only keep virus-infected cells in check, but can migrate to the brain and react with the body’s own proteins that trigger an autoimmune reaction in the case of MS.

"The most important genetic risk factor for MS therefore shapes a repertoire of T lymphocytes that responds very well to certain infectious agents such as Epstein-Barr virus and intestinal bacteria,” Martin said in a press release. "The disadvantage of this fitness is therefore that those affected also become susceptible to an immune response against their own brain tissue, which can lead to multiple sclerosis."

REFERENCE
Multiple sclerosis as the flip side of immune fitness. EurekAlert! https://www.eurekalert.org/pub_releases/2020-10/uoz-msa102220.php. Published October 22, 2020. Accessed October 23, 2020.