When infected with vaccinia virus engineered to produce MBP, the infection should activate the CD8+ T-cells to attack virally infected cells and also other cells that produce MBP. As expected, mice infected with the engineered virus developed MS-like disease but, surprisingly, symptoms were also triggered by infection with wild-type virus. This suggested that the engineered CD8+ T cells expressed a second receptor that recognised wild-type virus and subsequent cross-breeding experiments confirmed that some of the CD8+ T cells did indeed have receptors for both MBP and wild-type virus. Once activated by the virus, the dual-receptor CD8+ T cells were than able to attack cells producing MBP.
The study suggests a role for dual-receptor cells in autoimmune diseases and could explain how infection with a common virus triggers MS in genetically predisposed people, whilst having no lasting effects in most of the population. In the ‘dual-receptor model’, autoimmune activation could be triggered by a chance event leading to T-cells that recognise both MBP and a viral antigen. The prevalence of dual-receptor T cells is presently unclear and the team plan to assess whether they are more common in MS patients.
The study is published in Nature Immunology.