Cutting edge:: Induction of the antigen-processing enzyme IFN-γ-inducible lysosomal thiol reductase in melanoma cells is STAT1-dependent but CUTA-independent
Cutting edge:: Induction of the antigen-processing enzyme IFN-γ-inducible lysosomal thiol reductase in melanoma cells is STAT1-dependent but CUTA-independent
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DOI：
10.4049/jimmunol.173.2.731
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发表时间：
2004-07-15
影响因子：
4.4
通讯作者：
Blum, JS
中科院分区：
文献类型：
--
作者：
O'Donnell, PW;Haque, A;Blum, JS
在 MHC II 类分子的背景下，CD4(+) T 细胞对 Ag 的呈递和反应需要将天然蛋白质加工成短肽片段。在此途径中，IFN-γ诱导的溶酶体硫醇还原酶 (GILT) 的作用是催化硫醇键还原，从而展开天然蛋白 Ag 并促进通过细胞蛋白酶的进一步加工。与 B 细胞等专业 APC 相比，II 类阳性人类黑色素瘤表达的 GILT 蛋白或 mRNA 相对较少甚至不表达。 IFN-γ治疗后肿瘤细胞GILT表达部分恢复，但与II类Ag呈递所需的其他基因不同，GILT不受CIITA调节。相反，研究表明 STAT1 在 IFN-γ 诱导的 GILT 表达中发挥直接作用。这些结果定义了人类黑色素瘤中 MHC II 类基因和加工酶 GILT 解偶联调节的分子机制。
Presentation and CD4(+) T cell responses to Ag in the context of MHC class II molecules require processing of native proteins into short peptide fragments. Within this pathway, IFN-gamma-inducible lysosomal thiol reductase (GILT) functions-to catalyze thiol bond reduction, thus unfolding native protein Ag and facilitating further processing via cellular proteases. In contrast with professional APCs such as B cells, class II-positive human melanomas expressed relatively little to no GILT protein or mRNA. Tumor cell GILT expression was partially restored with IFN-gamma treatment but unlike other genes required for class II Ag presentation, GILT was not regulated by CIITA. Rather, studies revealed STAT1 plays a direct role in IFN-gamma-inducible GILT expression. These results define a molecular mechanism for the uncoupled regulation of MHC class II genes and the processing enzyme GILT in human melanomas.