An investigation of T cell adaptation in CNS autoimmune disease. (360G-Wellcome-085399_Z_08_Z)

The need for the immune system to maintain a broad T cell repertoire without developing an over-zealous reactivity to self antigens leading to autoimmunity is clear; this is broadly achieved through central and peripheral tolerogenic mechanisms with a huge amount of research being undertaken in recent years on the role of regulatory T cells in the maintenance of self tolerance. However, T cell adaptive tolerance, where a T cell senses antigenic cues from its environment and adjusts its threshold for full activation accordingly, has recently been shown to be an important tolerogenic mechanism yet has received little attention to date. The aim of this project is to more fully explore the mechanism of T cell adaptation. In particular, the longevity of the adapted T cell phenotype will be established and the role of CD5, which has been implicated as a potentially crucial molecule in adaptation, will be explored. In addition, how adapted T cells differ in their interactions with anitgen pre senting cells will be studied by multi-photon microscopy. Together, these studies will be valuable in clarifying the mechanism of T cell adaptation and the findings are likely to be highly relevant in our understanding of the maintenance of self tolerance.