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

ACS Chem Biol. 2017 Dec 15;12(12):3031-3038. doi: 10.1021/acschembio.7b00869. Epub 2017 Nov 10.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Gene Expression Regulation
  • Glycosylation
  • Mice
  • Proteins / metabolism*
  • Spleen / cytology


  • Proteins
  • Acetylglucosamine