Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells
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 recep...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/11765 |
| _version_ | 1828195383658938368 |
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| author | Ingeborg Streng-Ouwehand Nataschja I Ho Manja Litjens Hakan Kalay Martine Annemarie Boks Lenneke AM Cornelissen Satwinder Kaur Singh Eirikur Saeland Juan J Garcia-Vallejo Ferry A Ossendorp Wendy WJ Unger Yvette van Kooyk |
| author_facet | Ingeborg Streng-Ouwehand Nataschja I Ho Manja Litjens Hakan Kalay Martine Annemarie Boks Lenneke AM Cornelissen Satwinder Kaur Singh Eirikur Saeland Juan J Garcia-Vallejo Ferry A Ossendorp Wendy WJ Unger Yvette van Kooyk |
| author_sort | Ingeborg Streng-Ouwehand |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:41:28Z |
| format | Article |
| id | doaj.art-cc9b1971689946e283d4223a0cc25784 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:41:28Z |
| publishDate | 2016-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-cc9b1971689946e283d4223a0cc257842022-12-22T03:38:03ZengeLife Sciences Publications LtdeLife2050-084X2016-03-01510.7554/eLife.11765Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cellsIngeborg Streng-Ouwehand0Nataschja I Ho1Manja Litjens2Hakan Kalay3Martine Annemarie Boks4Lenneke AM Cornelissen5Satwinder Kaur Singh6Eirikur Saeland7Juan J Garcia-Vallejo8Ferry A Ossendorp9Wendy WJ Unger10Yvette van Kooyk11https://orcid.org/0000-0001-5997-3665Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsAntigen 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.https://elifesciences.org/articles/11765dendritic cellscross-presentationT cell primingglycosylationMGL1 |
| spellingShingle | Ingeborg Streng-Ouwehand Nataschja I Ho Manja Litjens Hakan Kalay Martine Annemarie Boks Lenneke AM Cornelissen Satwinder Kaur Singh Eirikur Saeland Juan J Garcia-Vallejo Ferry A Ossendorp Wendy WJ Unger Yvette van Kooyk Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells eLife dendritic cells cross-presentation T cell priming glycosylation MGL1 |
| title | Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells |
| title_full | Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells |
| title_fullStr | Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells |
| title_full_unstemmed | Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells |
| title_short | Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells |
| title_sort | glycan modification of antigen alters its intracellular routing in dendritic cells promoting priming of t cells |
| topic | dendritic cells cross-presentation T cell priming glycosylation MGL1 |
| url | https://elifesciences.org/articles/11765 |
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