White L C, Wright K L, Felix N J, Ruffner H, Reis L F, Pine R, Ting J P
University of North Carolina Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill 27599, USA.
Immunity. 1996 Oct;5(4):365-76. doi: 10.1016/s1074-7613(00)80262-9.
The TAP1 and LMP2 genes are central for class I MHC function and share a common promoter. Here, we analyze the molecular mechanism of IFN gamma up-regulation of TAP1 and LMP2. In vivo footprinting indicates IFN gamma up-regulates protein-DNA contacts at an IRF-E that is essential for the up-regulation of TAP1 and LMP2 by IFN gamma. Gel shift analysis indicates that this site binds IRF-1. The expression of TAP1 and LMP2 are both greatly reduced in IRF-1-deficient mice. Surface class I MHC as well as CD8+ T cells are reduced in IRF-1-/- mice. The role of IRF-1 in the regulation of TAP1 and LMP2 suggests a mechanism for the antiviral properties of IRF-1 and the unexpected deficiency of CD8+ T cells observed in IRF-1-/- mice.
TAP1和LMP2基因对于I类主要组织相容性复合体（MHC）的功能至关重要，且共享一个共同的启动子。在此，我们分析了干扰素γ（IFNγ）上调TAP1和LMP2的分子机制。体内足迹分析表明，IFNγ上调了位于干扰素调节因子元件（IRF-E）处的蛋白质-DNA相互作用，该元件对于IFNγ上调TAP1和LMP2至关重要。凝胶迁移分析表明，该位点结合干扰素调节因子1（IRF-1）。在IRF-1缺陷小鼠中，TAP1和LMP2的表达均大幅降低。在IRF-1基因敲除（IRF-1-/-）小鼠中，表面I类MHC以及CD8+ T细胞数量减少。IRF-1在调节TAP1和LMP2中的作用提示了IRF-1抗病毒特性的机制，以及在IRF-1-/-小鼠中观察到的CD8+ T细胞意外缺陷的机制。
