Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Immunity. 2010 Feb 26;32(2):279-89. doi: 10.1016/j.immuni.2010.01.013. Epub 2010 Feb 18.
Dendritic cell (DC) populations consist of multiple subsets that are essential orchestrators of the immune system. Technological limitations have so far prevented systems-wide accurate proteome comparison of rare cell populations in vivo. Here, we used high-resolution mass spectrometry-based proteomics, combined with label-free quantitation algorithms, to determine the proteome of mouse splenic conventional and plasmacytoid DC subsets to a depth of 5,780 and 6,664 proteins, respectively. We found mutually exclusive expression of pattern recognition pathways not previously known to be different among conventional DC subsets. Our experiments assigned key viral recognition functions to be exclusively expressed in CD4(+) and double-negative DCs. The CD8alpha(+) DCs largely lack the receptors required to sense certain viruses in the cytoplasm. By avoiding activation via cytoplasmic receptors, including retinoic acid-inducible gene I, CD8alpha(+) DCs likely gain a window of opportunity to process and present viral antigens before activation-induced shutdown of antigen presentation pathways occurs.
树突状细胞 (DC) 群体由多个亚群组成，这些亚群是免疫系统的重要协调者。技术限制迄今为止阻止了在体内对罕见细胞群体进行全面准确的蛋白质组比较。在这里，我们使用基于高分辨率质谱的蛋白质组学，结合无标记定量算法，分别对小鼠脾脏常规和浆细胞样 DC 亚群的蛋白质组进行了深度为 5780 和 6664 种蛋白质的分析。我们发现，模式识别途径的表达是相互排斥的，而这些途径以前在常规 DC 亚群中并不被认为是不同的。我们的实验将关键的病毒识别功能分配给 CD4(+) 和双阴性 DCs 进行表达。CD8alpha(+) DCs 很大程度上缺乏识别细胞质中某些病毒所需的受体。通过避免通过细胞质受体（包括视黄酸诱导基因 I）激活，CD8alpha(+) DCs 可能在抗原呈递途径激活诱导关闭之前获得处理和呈递病毒抗原的机会窗口。
