Role of microtubule acetylation in T cell activation and downstream function (IRC8P.450)

Abstract

Abstract Microtubules (MTs) play a number of important roles in antigen-mediated T cell activation and effector functions. Tubulin can undergo a number of post-translational modifications including acetylation of alpha tubulin. This acetylation affects MT growth dynamics and ability of motor proteins to traffic along them. We investigated the role of this acetylation in T cell function by using a mouse bearing deletion of the gene for alpha tubulin acetyltransferase 1 (aTAT1), the main acetyltransferase tubulin. Absence of aTAT1 leads to complete loss of acetylated alpha-tubulin. We found that CD4+ T cells from an aTAT1 deficient mouse showed more proliferation than controls upon stimulation with intermediate levels of antigen. We observed no difference in the level of calcium influx between WT and KO CD4+ T cells upon antigen stimulation. An important function of microtubules in CD8+ T cells is trafficking of cytolytic vesicles. Given that acetylation can affect the movement of motor proteins, we tested whether aTAT1 KO CD8+ and Natural Killer (NK) showed altered ability to kill target cells. These findings indicate that acetylation of alpha-tubulin is important in regulating T cell effector responses.