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.

中文翻译：

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免疫突触中的脂质开关


适应性免疫反应包括通过肽抗原激活 T 细胞，肽抗原由抗原呈递细胞表面的主要组织相容性复合体 (MHC) 的蛋白质呈递。 T 细胞受体与某种肽-MHC 复合物有效相互作用的结果是，一种称为免疫突触的特殊细胞-细胞连接形成，并伴随着细胞内信号分子的时空模式和功能的变化。活化 T 细胞中质子和内膜的细胞质小叶发生的关键修饰包括影响脂质双层内或附近蛋白质的结合和分布的脂质开关。在这里，我们描述了作用于这个关键的水/膜界面的两大类脂质开关。磷脂酰肌醇衍生自磷脂酰肌醇，磷脂酰肌醇是一种两亲性分子，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酶进行不同程度的磷酸化（去磷酸化），从而产生磷酸肌醇特征，从而定义信号分子、分子复合物或整个细胞器的组成和特性。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，从而改变蛋白质在膜上、膜间和膜内的分布。 T 细胞利用这两种类型的分子开关来调整其特性，以适应需要改变运动、运输、分泌和基因表达的激活过程。