During an acute infection, antigenic stimulation leads to activation, expansion, and differentiation of naïve CD8⁺ T cells, first into cytotoxic effector cells and eventually into long-lived memory cells. T cell antigen receptors (TCRs) detect antigens on antigen-presenting cells (APCs) in the form of antigenic peptides bound to major histocompatibility complex I (MHC-I)-encoded molecules and initiate TCR signal transduction network. This process is mediated by phosphorylation of many intracellular signaling proteins. Protein O-GlcNAc modification is another post-translational modification involved in this process, which often has either reciprocal or synergistic roles with phosphorylation. In this study, using a chemoenzymatic glycan labeling technique and proteomics analysis, we compared protein O-GlcNAcylation of murine effector and memory-like CD8⁺ T cells differentiated in vitro. By quantitative proteomics analysis, we identified 445 proteins that are significantly regulated in either effector- or memory-like T cell subsets. Furthermore, qualitative and quantitative analysis identified highly regulated protein clusters that suggest involvement of this post-translational modification in specific cellular processes. In effector-like T cells, protein O-GlcNAcylation is heavily involved in transcriptional and translational processes that drive fast effector T cells proliferation. During the formation of memory-like T cells, protein O-GlcNAcylation is involved in a more specific, perhaps more targeted regulation of transcription, mRNA processing, and translation. Significantly, O-GlcNAc plays a critical role as part of the “histone code” in both CD8⁺ T cells subgroups.

中文翻译：

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小鼠 CD8+ 效应和记忆样 T 细胞中蛋白质 O-GlcNAcylation 的分析

在急性感染期间，抗原刺激导致幼稚 CD8 ⁺ T 细胞的活化、扩增和分化，首先进入细胞毒性效应细胞，最终进入长寿命记忆细胞。T 细胞抗原受体 (TCR) 以与主要组织相容性复合物 I (MHC-I) 编码分子结合的抗原肽形式检测抗原呈递细胞 (APC) 上的抗原并启动 TCR 信号转导网络。这个过程是由许多细胞内信号蛋白的磷酸化介导的。蛋白O-GlcNAc 修饰是该过程中涉及的另一种翻译后修饰，通常与磷酸化具有互惠或协同作用。在这项研究中，我们使用化学酶聚糖标记技术和蛋白质组学分析，比较了体外分化的小鼠效应细胞和记忆样 CD8 ⁺ T 细胞的蛋白O -GlcNAcylation 。通过定量蛋白质组学分析，我们确定了 445 种蛋白质，这些蛋白质在效应子或记忆样 T 细胞亚群中受到显着调节。此外，定性和定量分析确定了高度调节的蛋白质簇，表明这种翻译后修饰参与了特定的细胞过程。在效应样 T 细胞中，蛋白O-GlcNAcylation 大量参与驱动快速效应 T 细胞增殖的转录和翻译过程。在记忆样 T 细胞的形成过程中，蛋白质O -GlcNAcylation 参与了对转录、mRNA 加工和翻译的更特异、可能更有针对性的调节。值得注意的是，O -GlcNAc 在 CD8 ⁺ T 细胞亚群中作为“组蛋白密码”的一部分起着至关重要的作用。