Profiling of Protein O-GlcNAcylation in Murine CD8+ Effector- and Memory-like T Cells

Aime Lopez Aguilar, Yu Gao, Xiaomeng Hou, Gregoire Lauvau, John R. Yates, Peng Wu

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3031-3038
Number of pages8
JournalACS Chemical Biology
Volume12
Issue number12
DOIs
StatePublished - Dec 15 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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