Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Blood. 2013 Feb 14;121(7):1145-56. doi: 10.1182/blood-2012-08-447409. Epub 2012 Dec 13.
Antigen presenting cells (APCs) that express a catalytically inactive version of the deubiquitylase YOD1 (YOD1-C160S) present exogenous antigens more efficiently to CD8(+) T cells, both in vitro and in vivo. Compared with controls, immunization of YOD1-C160S mice led to greater expansion of specific CD8(+) T cells and showed improved control of infection with a recombinant -herpes virus, MHV-68, engineered to express SIINFEKL peptide, the ligand for the ovalbumin-specific TCR transgenic OT-I cells. Enhanced expansion of specific CD8(+) T cells was likewise observed on infection of YOD1-C160S mice with a recombinant influenza A virus expressing SIINFEKL. YOD1-C160S APCs retained antigen longer than did control APCs. Enhanced crosspresentation by YOD1-C160S APCs was transporter associated with antigen processing (TAP1)-independent but sensitive to inclusion of inhibitors of acidification and of the proteasome. The activity of deubiquitylating enzymes may thus help control antigenspecific CD8(+) T-cell responses during immunization.
抗原呈递细胞 (APCs) 表达一种催化失活的去泛素酶 YOD1（YOD1-C160S），可更有效地将外源性抗原呈递给 CD8(+) T 细胞，无论是在体外还是体内。与对照组相比，YOD1-C160S 小鼠的免疫接种导致特定 CD8(+) T 细胞的扩增更大，并显示出对感染重组 - 疱疹病毒 MHV-68 的更好控制，该病毒工程表达 SIINFEKL 肽，是卵清蛋白特异性 TCR 转基因 OT-I 细胞的配体。在感染表达 SIINFEKL 的重组流感 A 病毒时，也观察到 YOD1-C160S APC 中特定 CD8(+) T 细胞的扩增增强。YOD1-C160S APC 保留抗原的时间长于对照 APC。YOD1-C160S APC 的增强交叉呈递与转运蛋白相关抗原加工 (TAP1) 无关，但对酸化和蛋白酶体抑制剂的包含敏感。因此，去泛素化酶的活性可能有助于控制免疫接种期间的抗原特异性 CD8(+) T 细胞反应。
