Format

Send to

Choose Destination
J Immunol. 2016 Oct 15;197(8):3086-3098. Epub 2016 Sep 21.

Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells.

Author information

1
Interdepartmental Program in Immunology, Stanford University, Stanford, CA 94305.
2
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.
3
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305.
4
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305; mmdavis@stanford.edu.
5
Stanford Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA 94305; and.
6
Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.

Abstract

T cell activation in response to Ag is largely regulated by protein posttranslational modifications. Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells.

PMID:
27655845
PMCID:
PMC5055199
DOI:
10.4049/jimmunol.1502031
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center