Wong Athena W, Brickey W June, Taxman Debra J, van Deventer Hendrick W, Reed William, Gao Jian Xin, Zheng Pan, Liu Yang, Li Ping, Blum Janice S, McKinnon Karen P, Ting Jenny P-Y
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Nat Immunol. 2003 Sep;4(9):891-8. doi: 10.1038/ni960. Epub 2003 Aug 10.
The major histocompatibility complex (MHC) class II transactivator (CIITA) is the 'master coactivator' of MHC class II genes. To identify new targets of CIITA, we analyzed cDNA microarrays of dendritic cells (DCs) from CIITA-deficient, MHC class II-deficient and control mice. We found the semaphorin receptor plexin-A1 was expressed in DCs, but not in other immune cells, and was strongly induced by CIITA. RNA interference by short hairpin RNA specific for plexin-A1, but not a single-nucleotide mutant, greatly reduced plexin-A1 expression and T cell stimulation by protein- or peptide-antigen-pulsed DCs.Plexin-A1 is not required for peptide binding to MHC. These data indicate involvement of plexin-A1 in T cell-DC interactions but not antigen processing or binding.
主要组织相容性复合体(MHC)II类反式激活因子(CIITA)是MHC II类基因的“主协同激活因子”。为了鉴定CIITA的新靶点,我们分析了来自CIITA缺陷、MHC II类缺陷和对照小鼠的树突状细胞(DC)的cDNA微阵列。我们发现,信号素受体丛状蛋白A1(plexin-A1)在DC中表达,但在其他免疫细胞中不表达,且受CIITA强烈诱导。用针对丛状蛋白A1的短发夹RNA而非单核苷酸突变体进行RNA干扰,可大幅降低丛状蛋白A1的表达以及蛋白或肽抗原脉冲DC对T细胞的刺激。肽与MHC结合不需要丛状蛋白A1。这些数据表明丛状蛋白A1参与T细胞与DC的相互作用,但不参与抗原加工或结合。