PDF(Pubmed)
Abstract：
Adaptive immune responses comprise the activation of T cells by peptide antigens that are presented by proteins of the Major Histocompatibility Complex (MHC) on the surface of an antigen-presenting cell. As a consequence of the T cell receptor interacting productively with a certain peptide-MHC complex, a specialized cell-cell junction known as the immunological synapse forms and is accompanied by changes in the spatiotemporal patterning and function of intracellular signaling molecules. Key modifications occurring at the cytoplasmic leaflet of the plasma and internal membranes in activated T cells comprise lipid switches that affect the binding and distribution of proteins within or near the lipid bilayer. Here, we describe two major classes of lipid switches that act at this critical water/membrane interface. Phosphoinositides are derived from phosphatidylinositol, an amphiphilic molecule that contains two fatty acid chains and a phosphate group that bridges the glycerol backbone to the carbohydrate inositol. The inositol ring can be variably (de-)phosphorylated by dedicated kinases and phosphatases, thereby creating phosphoinositide signatures that define the composition and properties of signaling molecules, molecular complexes, or whole organelles. Palmitoylation refers to the reversible attachment of the fatty acid palmitate to a substrate protein\'s cysteine residue. DHHC enzymes, named after the four conserved amino acids in their active site, catalyze this post-translational modification and thereby change the distribution of proteins at, between, and within membranes. T cells utilize these two types of molecular switches to adjust their properties to an activation process that requires changes in motility, transport, secretion, and gene expression.
摘要：
适应性免疫应答包括通过由抗原呈递细胞(APC)表面上的主要组织相容性复合物(MHC)的蛋白质呈递的肽抗原激活T细胞。由于T细胞受体（TCR）与某种肽-MHC复合物有效地相互作用，专门的细胞-细胞连接，免疫突触，形成并伴随着细胞内信号分子的时空模式和功能的变化。在活化的T细胞中的血浆和内膜的细胞质小叶处发生的关键修饰包括影响脂质双层内或附近的蛋白质的结合和分布的脂质开关。这里,我们描述了在这个关键的水/膜界面起作用的两大类脂质开关。磷酸肌醇衍生自磷脂酰肌醇，一种两亲性分子，含有两条脂肪酸链和一个将甘油主链与碳水化合物肌醇桥接的磷酸基团。肌醇环可以通过专用激酶和磷酸盐可变地（去）磷酸化，从而创建定义信号分子的组成和性质的磷酸肌醇特征，分子复合物或整个细胞器。棕榈酰化是指脂肪酸棕榈酸酯与底物蛋白的半胱氨酸残基的可逆连接。DHHC酶，以其活性位点的四个保守氨基酸命名，催化这种翻译后修饰，从而改变蛋白质的分布，膜之间和膜内。T细胞利用这两种类型的分子开关来调整它们的特性以适应需要运动变化的激活过程，运输,分泌和基因表达。
