Serrador Juan M, Cabrero Jose Román, Sancho David, Mittelbrunn María, Urzainqui Ana, Sánchez-Madrid Francisco
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, E-28006 Madrid, Spain.
Immunity. 2004 Apr;20(4):417-28. doi: 10.1016/s1074-7613(04)00078-0.
We investigated the role of acetylated microtubules in the antigen-specific interaction of T helper and antigen-presenting cells (APCs). In T cells, acetylated microtubules concentrated at contact site with APCs, surrounding clusters of CD3 and LFA-1. TcR engagement induced a transient deacetylation of microtubules at early times and an enhanced acetylation at late times. Confocal videomicroscopy studies revealed that the HDAC6 tubulin deacetylase was translocated and concentrated at the contact site of T cells with APCs. Overexpression of HDAC6 but not a dead deacetylase mutant in T cells disorganized CD3 and LFA-1 at the immune synapse. This effect was reverted by treatment with the deacetylase inhibitor trichostatin A. The antigen-specific translocation of the microtubule organizing center (MTOC) and IL-2 production were also severely impaired by overexpression of HDAC6. Our results underscore the key role for HDAC6 in the organization of the immune synapse and the antigen-specific reorientation of the MTOC.
我们研究了乙酰化微管在辅助性T细胞与抗原呈递细胞（APC）的抗原特异性相互作用中的作用。在T细胞中，乙酰化微管集中在与APC的接触部位，围绕着CD3和LFA-1簇。T细胞受体（TcR）的激活在早期诱导微管的短暂去乙酰化，并在后期增强乙酰化。共聚焦视频显微镜研究显示，HDAC6微管蛋白去乙酰化酶转位并集中在T细胞与APC的接触部位。在T细胞中过表达HDAC6而不是失活的去乙酰化酶突变体，会使免疫突触处的CD3和LFA-1紊乱。用去乙酰化酶抑制剂曲古抑菌素A处理可逆转这种效应。微管组织中心（MTOC）的抗原特异性转位和白细胞介素-2的产生也因HDAC6的过表达而严重受损。我们的结果强调了HDAC6在免疫突触组织和MTOC的抗原特异性重新定向中的关键作用。
