Mgat2 ablation in the myeloid lineage leads to defective glycoantigen T cell responses

Academic Article


  • N-linked glycosylation is a central regulatory factor that influences the immune system in varied and profound ways, including leukocyte homing, T cell receptor signaling and others. Moreover, N-glycan branching has been demonstrated to change as a function of infection and inflammation. Our previous findings suggest that complex-type N-glycans on the class II major histocompatibility complex play an important role in antigen selection within antigen presenting cells (APCs) such that highly branched N-glycans promote polysaccharide (glycoantigen, GlyAg) presentation following Toll-like receptor 2 (TLR2)-dependent antigen processing. In order to explore the impact of N-glycan branching on the myeloid-derived APC population without the confounding problems of altering the branching of lymphocytes and non-hematopoietic cells, we created a novel myeloid-specific knockout of the -1,2-N- acetylglucosaminyltransferase II (Mgat2) enzyme. Using this novel mouse, we found that the reduction in multi-antennary N-glycans characteristic of Mgat2 ablation had no impact on GlyAg-mediated TLR2 signaling. Likewise, no deficits in antigen uptake or cellular homing to lymph nodes were found. However, we discovered that Mgat2 ablation prevented GlyAg presentation and T cell activation in vitro and in vivo without apparent alterations in protein antigen response or myeloid-mediated protection from infection. These findings demonstrate that GlyAg presentation can be regulated by the N-glycan branching pattern of APCs, thereby establishing an in vivo model where the T cell-dependent activity of GlyAgs can be experimentally distinguished from GlyAg-mediated stimulation of the innate response through TLR2. © 2013 Published by Oxford University Press.
  • Authors

    Published In

  • Glycobiology  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 11848332
  • Author List

  • Ryan SO; Leal SM; Abbott DW; Pearlman E; Cobb BA
  • Start Page

  • 262
  • End Page

  • 271
  • Volume

  • 24
  • Issue

  • 3