Analysis of the mechanisms of discrimination, recognition and response to food proteins by the immune system

1.研究了口服耐受T细胞的特性及其低反应性的分子机制。我们阐明了口服耐受性T细胞的以下特征。由于caspase的激活，口服耐受的T细胞不能形成与GADS-SLP-76相关的正常TCR信号复合体。口服耐受的T细胞表现出TcR、PKC-θ和脂筏移位到T细胞和APC之间的界面的缺陷，以及VaV激活的障碍。因此，口服耐受的T细胞在免疫突触形成方面存在缺陷。此外，口服耐受T细胞中蛋白磷酸酶SHP-1的表达上调。这些观察结果可能解释了口服耐受T细胞的低反应状态。我们还发现，根据CD44/CD62L、CD62L^&lt；High&gt；CD44^&lt；low&gt；细胞和CD62L^&lt；low&gt；CD44^&lt；High&gt；细胞的表达情况，可以将口服耐受小鼠的T细胞分为两类。这些细胞群既有低反应性，又具有免疫调节功能。然而，它们在细胞因子的分泌能力和抑制方式上有所不同。结果表明，口服抗原诱导了两种不同类型的具有免疫调节功能的低反应性T细胞，这两种细胞表面分子的表达可以区分开来。2.口服生物素标记的抗原，用荧光标记的亲和素检测抗原提呈。结果表明，B220 Peyer‘s斑块树突状细胞具有口服抗原性。3.建立并分析了无菌T细胞受体转基因小鼠。结果表明，肠道共生菌对肠道免疫系统的T细胞因子反应有影响。

1.The characteristics of orally tolerized T cells and the molecular mechanisms of their hyporesponsiveness was investigated. We elucidated the following characteristics of orally tolerant T cells. As a consequence of caspase activation, orally tolerant T cells could not form normal TCR signaling complexes associated with GADS-SLP-76. Orally-tolerized T cells showed defects in the translocation of TCR, PKC-θ, and lipid rafts into the interface between T cells and APCs, as well as impairment in vav activation. Thus orally-tolerized T cells were defective in immunological synapse formation. Furthermore, the expression of the protein phosphatase SHP-1 was upregulated in orally tolerized T cells. These observations may account for the hyporesponsive state of orally-tolerized T cells. We also found that T cells from orally tolerant mice could be divided into two populations based on the expression of CD44/CD62L, CD62L^<high>CD44^<low> cells and CD62L^<low>CD44^<high> cells. These cell populations were both hyporesponsive and possessed immunoregulatory functions. Nevertheless, they differed in cytokine secreting capacity and mode of suppression. The results suggested that oral administration of antigen induced two distinct types of hyporesponsive T cells with immunoregulatory function, that could be distinguished by expression of these cell surface molecules.2.Mice were orally administered with biotinylated antigen and antigen presentation was detected by fluorescence-labeled avidin. The results suggested that B220^+ Peyer's patch dendritic cells presented oral antigen.3.Germ-free T cell receptor transgenic mice were established and analyzed. It was shown that commensal bacteria affected the T cell cytokine response in the intestinal immune system.