School of Medicine, University of St Andrews, Fife, UK.
Immunology. 2012 Feb;135(2):133-9. doi: 10.1111/j.1365-2567.2011.03518.x.
Many MHC class I molecules contain unpaired cysteine residues in their cytoplasmic tail domains, the function of which remains relatively uncharacterized. Recently, it has been shown that in the small secretory vesicles known as exosomes, fully folded MHC class I dimers can form through a disulphide bond between the cytoplasmic tail domain cysteines, induced by the low levels of glutathione in these extracellular vesicles. Here we address whether similar MHC class I dimers form in whole cells by alteration of the redox environment. Treatment of the HLA-B27-expressing Epstein-Barr virus-transformed B-cell line Jesthom, and the leukaemic T-cell line CEM transfected with HLA-B27 with the strong oxidant diamide, and the apoptosis-inducing and glutathione-depleting agents hydrogen peroxide and thimerosal, induced MHC class I dimers. Furthermore, induction of apoptosis by cross-linking FasR/CD95 on CEM cells with monoclonal antibody CH-11 also induced MHC class I dimers. As with exosomal MHC class I dimers, the formation of these structures on cells is controlled by the cysteine at position 325 in the cytoplasmic tail domain of HLA-B27. Therefore, the redox environment of cells intimately controls induction of MHC class I dimers, the formation of which may provide novel structures for recognition by the immune system.
许多 MHC I 类分子在其胞质尾部含有不成对的半胱氨酸残基，但其功能仍相对未知。最近，研究表明，在称为外泌体的小分泌小泡中，通过胞质尾部半胱氨酸之间的二硫键，完全折叠的 MHC I 二聚体可以形成，这是由这些细胞外囊泡中谷胱甘肽水平低引起的。在这里，我们通过改变氧化还原环境来研究是否在整个细胞中形成类似的 MHC I 二聚体。用强氧化剂二酰胺处理 HLA-B27 表达的 Epstein-Barr 病毒转化的 B 细胞系 Jesthom 和转染 HLA-B27 的白血病 T 细胞系 CEM，以及诱导细胞凋亡和耗尽谷胱甘肽的试剂过氧化氢和硫柳汞，诱导 MHC I 二聚体形成。此外，用单克隆抗体 CH-11 交联 CEM 细胞上的 FasR/CD95 诱导细胞凋亡也诱导了 MHC I 二聚体的形成。与外泌体 MHC I 二聚体一样，这些结构在细胞上的形成受 HLA-B27 胞质尾部第 325 位半胱氨酸控制。因此，细胞的氧化还原环境密切控制 MHC I 二聚体的诱导，其形成可能为免疫系统的识别提供新的结构。
