Diet and autoimmunity: modulation of the myelin oligodendrocyte glycoprotein specific T cell repertoire by the milk protein butyrophilin. (360G-Wellcome-081648_Z_06_Z)

Sensitisation to the milk protein butyrophilin1A1 (BTN) initiates an immune response that cross-reacts with myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in multiple sclerosis (MS). This cross reactivity can be exploited to expand regulatory T cell populations that suppress the encephalitogenic potential of MOG-specific T cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This project will exploit the availability of BTN deficient C57 BL/6 mice to test the hypothesis that epitopes derived from autologous BTN play a major role in shaping the composition/function of the endogenous MOG-reactive autoimmune T cell repertoire. Specifically, we will investigate: (1) The mechanism(s) by which immunological self-tolerance to autologous BTN is established. (2) How epitopes derived from autologous BTN influence the composition/function of the MOG-reactive T cell repertoire and susceptibility to MOG-induced EAE. (3) How sens itisation to autologous BTN may be exploited to suppress MOG-mediated autoaggression in adults.