Influence of Glycosylation Inhibition on the Binding of KIR3DL1 to HLA-B*57:01.


Viral infections can affect the glycosylation pattern of glycoproteins involved in antiviral immunity. Given the importance of protein glycosylation for immune function, we investigated the effect that modulation of the highly conserved HLA class I N-glycan has on KIR:HLA interactions and NK cell function. We focused on HLA-B57:01 and its interaction with KIR3DL1, which has been shown to play a critical role in determining the progression of a number of human diseases, including human immunodeficiency virus-1 infection. 721.221 cells stably expressing HLA-B57:01 were treated with a panel of glycosylation enzyme inhibitors, and HLA class I expression and KIR3DL1 binding was quantified. In addition, the functional outcomes of HLA-B57:01 N-glycan disruption/modulation on KIR3DL1ζ+ Jurkat reporter cells and primary human KIR3DL1+ NK cells was assessed. Different glycosylation enzyme inhibitors had varying effects on HLA-B57:01 expression and KIR3DL1-Fc binding. The most remarkable effect was that of tunicamycin, an inhibitor of the first step of N-glycosylation, which resulted in significantly reduced KIR3DL1-Fc binding despite sustained expression of HLA-B57:01 on 721.221 cells. This effect was paralleled by decreased activation of KIR3DL1ζ+ Jurkat reporter cells, as well as increased degranulation of primary human KIR3DL1+ NK cell clones when encountering HLA-B57:01-expressing 721.221 cells that were pre-treated with tunicamycin. Overall, these results demonstrate that N-glycosylation of HLA class I is important for KIR:HLA binding and has an impact on NK cell function.





Published Version (Please cite this version)


Publication Info

Salzberger, Wilhelm, Wilfredo F Garcia-Beltran, Haley Dugan, Supreetha Gubbala, Camille Simoneau, Simon B Gressens, Stephanie Jost, Marcus Altfeld, et al. (2015). Influence of Glycosylation Inhibition on the Binding of KIR3DL1 to HLA-B*57:01. PloS one, 10(12). p. e0145324. 10.1371/journal.pone.0145324 Retrieved from

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



Stephanie Rachel Jost

Associate Professor in Surgery

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.