CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells
CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells
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DOI：
10.1128/mcb.25.17.7743-7757.2005
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发表时间：
2005-09-01
影响因子：
5.3
通讯作者：
Morimoto, C
中科院分区：
文献类型：
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作者：
Ohnuma, K;Yamochi, T;Morimoto, C
CD 26是一种T细胞共刺激分子，在其细胞外区域具有二肽基肽酶IV酶活性。我们以前曾报道，添加重组可溶性CD 26导致增强的人T淋巴细胞的增殖诱导的召回抗原破伤风类毒素（TT）通过上调单核细胞上的CD 86和小窝蛋白-1是一个结合蛋白的CD 26，和CD 26-小窝蛋白-1相互作用导致小窝蛋白-1磷酸化（p-cav-1）以及TT介导的T细胞增殖。然而，这种免疫增强的机制尚未阐明。在目前的工作中，我们进行实验，以确定p-cav-1直接导致CD 86上调的分子机制。通过蛋白质组学分析，我们确定Tollip（Toll相互作用蛋白）和IRAK-1（白细胞介素-1受体相关的丝氨酸/苏氨酸激酶1）作为小窝蛋白-1相互作用的蛋白质在单核细胞。我们还证明了外源性CD 26刺激后，Tollip和IRAK-1从小窝蛋白-1解离，然后IRAK-1在胞质溶胶中磷酸化，通过激活NF-κ B导致CD 86上调。因此，CD 26与小窝蛋白-1的结合调节抗原呈递细胞中的信号传导途径以诱导抗原特异性T细胞增殖。
CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV enzyme activity in its extracellular region. We have previously reported that the addition of recombinant soluble CD26 resulted in enhanced proliferation of human T lymphocytes induced by the recall antigen tetanus,toxoid (TT) via upregulation of CD86 on monocytes and that caveolin-1 was a binding protein of CD26, and the CD26-caveolin-1 interaction resulted in caveolin-1 phosphorylation (p-cav-1) as well as TT-mediated T-cell proliferation. However, the mechanism involved in this immune enhancement has not yet been elucidated. In the present work, we perform experiments to identify the molecular mechanisms by which p-cav-1 leads directly to the upregulation of CD86. Through proteomic analysis, we identify Tollip (Toll-interacting protein) and IRAK-1 (interleukin-1 receptor-associated serine/threonine kinase 1) as caveolin-l-interacting proteins in monocytes. We also demonstrate that following stimulation by exogenous CD26, Tollip and IRAK-1 dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol, leading to the upregulation of CD86 via activation of NF-kappa B. Binding of CD26 to caveolin-1 therefore regulates signaling pathways in antigen-presenting cells to induce antigen-specific T-cell proliferation.