Zheng Hong, Li Zihai
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
J Immunol. 2004 Nov 15;173(10):5929-33. doi: 10.4049/jimmunol.173.10.5929.
The ability for the professional APC to cross-present Ag to MHC class I from parenchymal cells is essential for priming as well as tolerance of CD8+ T cells against intracellular Ags. Since cross-presentations of non-cell-associated free Ags are inefficient, the roles of molecular chaperones or heat shock proteins (HSPs) in chaperoning Ags to APCs have been postulated. We herein genetically addressed this hypothesis using mice that were defective of heat shock factor 1 (Hsf1), a major transcription factor for HSPs. Hsf1(-/-) mice have a decreased expression of several HSPs including HSP90 and HSP70. Using multiple Ag systems, we demonstrated that cross-priming of Ag-specific CD8+ T cells was inefficient when Ag expression was restricted to Hsf1(-/-) non-APCs. Our study provides the first genetic evidence for the roles of Hsf1 in regulating cross-presentation of MHC class I-associated Ags.
专业抗原呈递细胞（APC）将抗原从实质细胞交叉呈递给MHC I类分子的能力对于启动以及CD8 + T细胞对细胞内抗原的耐受性至关重要。由于非细胞相关游离抗原的交叉呈递效率低下，因此推测分子伴侣或热休克蛋白（HSP）在将抗原伴侣至APC中的作用。我们在此使用热休克因子1（Hsf1）缺陷的小鼠对这一假设进行了基因研究，Hsf1是HSP的主要转录因子。Hsf1（-/-）小鼠中包括HSP90和HSP70在内的几种HSP的表达降低。使用多种抗原系统，我们证明当抗原表达仅限于Hsf1（-/-）非APC时，抗原特异性CD8 + T细胞的交叉启动效率低下。我们的研究为Hsf1在调节MHC I类相关抗原的交叉呈递中的作用提供了首个遗传学证据。
