Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Immunol Cell Biol. 2012 Oct;90(9):841-51. doi: 10.1038/icb.2012.29. Epub 2012 Jul 17.
Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (GrB) that protects activated cytotoxic lymphocytes from apoptosis. We show here that the CD8(+) subset of splenic dendritic cells (DC), specialized in major histocompatibility complex class I (MHC I) presentation of exogenous antigens (cross-presentation), produce high levels of Sb9. Mice deficient in Sb9 are unable to generate a cytotoxic T-cell response against cell-associated antigen by cross-presentation, but maintain normal MHC-II presentation to helper T cells. This impaired cross-priming ability is autonomous to DC and is evident in animals deficient in both Sb9 and GrB, indicating that this role of Sb9 in DC is GrB-independent. In Sb9-deficient mice, CD8(+) DC develop normally, survive as well as wild-type DC after antigenic challenge, and exhibit unimpaired capacity to take up antigen. Although the core processing machinery is unaffected, Sb9-deficient DC appear to process antigen faster. Our results point to a novel, GrB-independent role for Sb9 in DC cross-priming.
丝氨酸蛋白酶抑制剂 B9（Sb9，也称为 Spi6）是一种细胞内的颗粒酶 B（GrB）抑制剂，可保护激活的细胞毒性淋巴细胞免于凋亡。我们在此表明，脾脏树突状细胞（DC）的 CD8+亚群专门表达 MHC I 类（MHC I）外源性抗原（交叉呈递），产生高水平的 Sb9。缺乏 Sb9 的小鼠无法通过交叉呈递对细胞相关抗原产生细胞毒性 T 细胞反应，但仍能正常呈递 MHC-II 类给辅助性 T 细胞。这种受损的交叉引发能力是 DC 自主的，在缺乏 Sb9 和 GrB 的动物中均明显，表明 Sb9 在 DC 中的这种作用与 GrB 无关。在缺乏 Sb9 的小鼠中，CD8+DC 正常发育，在抗原刺激后与野生型 DC 一样存活，并表现出摄取抗原的能力未受损。尽管核心加工机制不受影响，但缺乏 Sb9 的 DC 似乎更快地加工抗原。我们的研究结果表明，Sb9 在 DC 交叉引发中具有一种新的、GrB 无关的作用。
