Defective antigen processing in GILT-free mice
Defective antigen processing in GILT-free mice
复制标题
DOI：
10.1126/science.1065500
复制
发表时间：
2001-11-09
期刊：
影响因子：
56.9
通讯作者：
Cresswell, P
中科院分区：
文献类型：
--
作者：
Maric, M;Arunachalam, B;Cresswell, P
主要组织相容性复合物 (MHC) II 类限制性呈递给 CD4 阳性 T 淋巴细胞的蛋白质加工过程发生在它们被抗原呈递细胞 (APC) 内化后。抗原蛋白通常含有二硫键，它们在内吞途径中的减少有利于加工。在人类中，γ干扰素诱导型溶酶体硫醇还原酶 (GILT) 组成型存在于 APC 的晚期内吞区室中。在这里，我们鉴定了 GILT 的小鼠同源物并生成了 GILT 敲除小鼠。 GILT 促进含有二硫键的蛋白质抗原的加工和呈递给抗原特异性 T 细胞。详细检查了对鸡蛋溶菌酶（一种具有包含四个二硫键的紧凑结构的模型抗原）的反应。
Processing of proteins for major histocompatibility complex (MHC) class II-restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins frequently contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compartments of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to antigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact Structure containing four disulfide bonds, was examined in detail.