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 II. 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.

译文

:IFN-γ诱导的溶酶体硫醇还原酶(GILT)是独特的硫醇还原酶,在低pH值下具有最佳的酶促活性。 GILT在展开抗原蛋白以进行蛋白水解切割和通过MHC II类呈递所得肽的过程中起着至关重要的作用。在这项研究中,我们证明了GILT在T淋巴细胞中表达,并且在T细胞活化的调节中具有APC无关的作用。出人意料的是,在体外比较野生型和GILT缺陷型T细胞的激活情况显示,在没有GILT的情况下,其反应性更强。 GILT减少增殖和细胞毒性反应的作用是T细胞内源性的,是由于单个细胞水平的敏感性降低所致。因此,主要具有溶酶体定位的分子可抑制T细胞活化,该过程的特征是信号从质膜传递到细胞质和细胞核。

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