E3 ubiquitin ligases and their control of T cell autoreactivity

A loss of T cell tolerance underlies the development of most autoimmune diseases. The design of therapeutic strategies to re-institute immune tolerance, however, is hampered by uncertainty regarding the molecular mechanisms involved in the inactivation of potentially autoreactive T cells. Recently, E3 ubiquitin ligases have been shown to mediate the development of a durable state of unresponsiveness in T cells called clonal anergy. In this review, we will discuss the mechanisms used by E3 ligases to control the activation of T cells and prevent the development of autoimmunity.