Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic stimulation.
Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic stimulation.
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DOI：
10.1084/jem.185.10.1859
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发表时间：
1997-05-19
期刊：
影响因子：
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通讯作者：
Lanzavecchia A
中科院分区：
文献类型：
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作者：
Valitutti S;Müller S;Salio M;Lanzavecchia A
通过特异性抗原的T细胞活化导致触发的T细胞受体（TCR）的快速且持久的下调。在这项工作中，我们研究了下调的TCR-CD 3-CD 4复合物的命运。由肽脉冲的抗原呈递细胞（APC）刺激的T细胞经历TCR-β、CD 3-ε和CD 3-ε链的总细胞含量的抗原剂量依赖性降低，如通过对固定和透化的T-APC缀合物的FACS®分析和通过对细胞裂解物的蛋白质印迹分析所检测的。CD 3-β链消耗的时间过程与TCR下调的时间过程重叠，表明内化的TCR-CD 3复合物迅速降解。溶酶体功能抑制剂（巴弗洛霉素A1，福利霉素）显着减少β链降解，导致β链的积累在大的Lamp 1+囊泡。这些结果表明，在T细胞-APC缀合物中，触发的TCR从细胞表面快速去除并在溶酶体区室中降解。
T cell activation by specific antigen results in a rapid and long-lasting downregulation of triggered T cell receptors (TCRs). In this work, we investigated the fate of downregulated TCR– CD3-ζ complexes. T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-β, CD3-ε, and ζ chains, as detected by FACS® analysis on fixed and permeabilized T–APC conjugates and by Western blot analysis on cell lysates. The time course of CD3-ζ chain consumption overlaps with that of TCR downregulation, indicating that internalized TCR–CD3 complexes are promptly degraded. Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced ζ chain degradation, leading to the accumulation of ζ chain in large Lamp1+ vesicles. These results indicate that in T cell–APC conjugates, triggered TCRs are rapidly removed from the cell surface and are degraded in the lysosomal compartment.