Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse: Involvement of SNARE complexes
Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse: Involvement of SNARE complexes
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DOI：
10.1016/s1074-7613(04)00106-2
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发表时间：
2004-05-01
期刊：
影响因子：
32.4
通讯作者：
Alcover, A
中科院分区：
文献类型：
--
作者：
Das, V;Nal, B;Alcover, A
T细胞抗原受体（TCR）在免疫突触处积聚的机制尚未完全阐明。由于TCR持续内化并再循环回到细胞表面，我们研究了极化再循环在TCR靶向免疫突触中的作用。我们在这里表明，T细胞遇到活化抗原呈递细胞（APC）的再循环内体区室向T细胞-APC接触部位极化。此外，通过再循环内体转运的TCR靶向免疫突触。抑制T细胞极性、组成性TCR内吞或再循环可减少免疫突触处的TCR积累。相反，在突触形成之前增加再循环内体中TCR的量增强了它们的积累。最后，我们表明，从T细胞的外排t-SNARE集群在APC接触网站和破伤风毒素抑制TCR积累在免疫突触，表明囊泡融合介导的SNARE复合物参与TCR靶向免疫突触。
The mechanism by which T cell antigen receptors (TCR) accumulate at the immunological synapse has not been fully elucidated. Since TCRs are continuously internalized and recycled back to the cell surface, we investigated the role of polarized recycling in TCR targeting to the immunological synapse. We show here that the recycling endosomal compartment of T cells encountering activatory antigen-presenting cells (APCs) polarizes towards the T cell-APC contact site. Moreover, TCRs in transit through recycling endosomes are targeted to the immunological synapse. Inhibition of T cell polarity, constitutive TCR endocytosis, or recycling reduces TCR accumulation at the immunological synapse. Conversely, increasing the amount of TCRs in recycling endosomes before synapse formation enhanced their accumulation. Finally, we show that exocytic t-SNAREs from T cells cluster at the APC contact site and that tetanus toxin inhibits TCR accumulation at the immunological synapse, indicating that vesicle fusion mediated by SNARE complexes is involved in TCR targeting to the immunological synapse.