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.
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