Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells

eLife

Nataschja I Ho¹  Ferry A Ossendorp¹  Manja Litjens²  Hakan Kalay²  Martine Annemarie Boks²  Lenneke AM Cornelissen²  Yvette van Kooyk²  Wendy WJ Unger²  Satwinder Kaur Singh²  Eirikur Saeland²  Juan J Garcia-Vallejo²  Ingeborg Streng-Ouwehand² 

[1] Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands;Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands;

关键词: dendritic cells;    cross-presentation;    T cell priming;    glycosylation;    MGL1;   

DOI  :  10.7554/eLife.11765

来源: DOAJ

【 摘 要 】

Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated by C-type lectin receptors that recognize glycan structures. We show that the modification of Ovalbumin (OVA) with the glycan-structure LewisX (LeX) re-directs OVA to the C-type lectin receptor MGL1. LeX-modification of OVA favored Th1 skewing of CD4+ T cells and enhanced cross-priming of CD8+ T cells. While cross-presentation of native OVA requires high antigen dose and TLR stimuli, LeX modification reduces the required amount 100-fold and obviates its dependence on TLR signaling. The OVA-LeX-induced enhancement of T cell cross-priming is MGL1-dependent as shown by reduced CD8+ effector T cell frequencies in MGL1-deficient mice. Moreover, MGL1-mediated cross-presentation of OVA-LeX neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intracellular storage of antigen in Rab11+LAMP1+ compartments. We conclude that controlled neo-glycosylation of antigens can crucially influence intracellular routing of antigens, the nature and strength of immune responses and should be considered for optimizing current vaccination strategies.

【 授权许可】

Unknown