Turning over the Chance card on MS susceptibility

Nature Immunology 11, 570 - 572 (2010) doi:10.1038/ni0710-570

CD8⁺ T cells expressing two distinct T cell antigen receptors fail to be tolerized and can induce autoimmunity.

In this issue of Nature Immunology, Goverman and colleagues present an intricate series of experiments whose results identify a previously unknown mechanism by which T cell antigen receptor (TCR)-transgenic CD8⁺ anti-myelin T cells can be induced to break tolerance and cause severe demyelination¹. Although the model relies on cutting-edge technology and an engineered immune system, the underlying scheme shown here may be surprisingly relevant for the pathogenesis of the most prevalent human demyelinating disease, multiple sclerosis.