Inhibitory role of IFN-γ-inducible lysosomal thiol reductase in T cell activation
Inhibitory role of IFN-γ-inducible lysosomal thiol reductase in T cell activation
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DOI：
10.4049/jimmunol.177.7.4369
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Maric, Maja
中科院分区：
文献类型：
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作者：
Barjaktarevic, Igor;Rahman, Ayman;Maric, Maja
IFN-γ诱导的溶酶体巯基还原酶（GILT）是一种独特的巯基还原酶，在低pH下具有最佳的酶活性。GILT在抗原蛋白的解折叠中起着至关重要的作用，以准备其蛋白水解切割和由MHC H类呈递所得肽。在这项研究中，我们证明，GILT是在T淋巴细胞中表达，它有APC非相关的作用，在调节T细胞活化。令人惊讶的是，野生型和GILT缺陷型T细胞体外活化的比较揭示了在GILT不存在的情况下更强的反应性。GILT在降低增殖和细胞毒性反应中的作用是T细胞内源性的，并且是由单个细胞水平的敏感性降低引起的。因此，主要具有溶酶体定位的分子抑制T细胞活化，这是一个以从质膜到细胞质和细胞核的信号传递为特征的过程。
IFN-gamma-inducible lysosomal thiol reductase (GILT) is a unique thiol reductase with optimal enzymatic activity at low pH. GILT plays a crucial role in unfolding the antigenic proteins in preparation for their proteolytic cleavage and presentation of resulting peptides by MHC class H. In this study, we demonstrate that GILT is expressed in T lymphocytes and that it has an APC-nonrelated role in the regulation of T cell activation. Surprisingly, comparison of wild-type and GILT-deficient T cell activation in vitro revealed stronger responsiveness in the absence of GILT. The effect of GILT in reducing the proliferative and cytotoxic responses was endogenous to T cells and resulted from decreased sensitivity at the individual cell level. Therefore, a molecule with primarily lysosomal localization suppresses T cell activation, a process characterized by signal transmission from plasma membrane to cytoplasm and nucleus.