Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T‐cell activation
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- Rodney A. Rosalia
- Department of Clinical Pharmacy and Toxicology Leiden University Medical Center Leiden The Netherlands
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- Esther D. Quakkelaar
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Anke Redeker
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Selina Khan
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Marcel Camps
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Jan W. Drijfhout
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Ana Luisa Silva
- Division of Drug Delivery Technology Leiden Academic Centre for Drug Research Leiden University Medical Center Leiden The Netherlands
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- Wim Jiskoot
- Division of Drug Delivery Technology Leiden Academic Centre for Drug Research Leiden University Medical Center Leiden The Netherlands
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- Thorbald van Hall
- Department of Clinical Oncology Leiden University Medical Center Leiden The Netherlands
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- Peter A. van Veelen
- Department of Molecular Cell Biology Leiden University Medical Center Leiden The Netherlands
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- George Janssen
- Department of Molecular Cell Biology Leiden University Medical Center Leiden The Netherlands
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- Kees Franken
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Luis J. Cruz
- Department of Endocrinology Leiden University Medical Center Leiden The Netherlands
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- Angelino Tromp
- Department of Endocrinology Leiden University Medical Center Leiden The Netherlands
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- Jaap Oostendorp
- Department of Clinical Pharmacy and Toxicology Leiden University Medical Center Leiden The Netherlands
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- Sjoerd H. van der Burg
- Department of Clinical Oncology Leiden University Medical Center Leiden The Netherlands
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- Ferry Ossendorp
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
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- Cornelis J. M. Melief
- Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands
Description
<jats:p>The efficiency of antigen (<jats:styled-content style="fixed-case">A</jats:styled-content>g) processing by dendritic cells (<jats:styled-content style="fixed-case">DC</jats:styled-content>s) is vital for the strength of the ensuing <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (<jats:styled-content style="fixed-case">SLP</jats:styled-content>s) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of <jats:styled-content style="fixed-case">SLP</jats:styled-content>s. We report an in vitro processing analysis of <jats:styled-content style="fixed-case">SLP</jats:styled-content>s for <jats:styled-content style="fixed-case">MHC</jats:styled-content> class I and class II presentation by murine <jats:styled-content style="fixed-case">DC</jats:styled-content>s and human monocyte‐derived <jats:styled-content style="fixed-case">DC</jats:styled-content>s. Compared to protein, <jats:styled-content style="fixed-case">SLP</jats:styled-content>s were rapidly and much more efficiently processed by <jats:styled-content style="fixed-case">DC</jats:styled-content>s, resulting in an increased presentation to <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup> and <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">T</jats:styled-content> cells. The mechanism of access to <jats:styled-content style="fixed-case">MHC</jats:styled-content> class I loading appeared to differ between the two forms of <jats:styled-content style="fixed-case">A</jats:styled-content>g. Whereas whole soluble protein <jats:styled-content style="fixed-case">A</jats:styled-content>g ended up largely in endolysosomes, <jats:styled-content style="fixed-case">SLP</jats:styled-content>s were detected very rapidly outside the endolysosomes after internalization by <jats:styled-content style="fixed-case">DC</jats:styled-content>s, followed by proteasome‐ and transporter associated with Ag processing‐dependent <jats:styled-content style="fixed-case">MHC</jats:styled-content> class I presentation. Compared to the slower processing route taken by whole protein <jats:styled-content style="fixed-case">A</jats:styled-content>gs, our results indicate that the efficient internalization of <jats:styled-content style="fixed-case">SLP</jats:styled-content>s, accomplished by <jats:styled-content style="fixed-case">DC</jats:styled-content>s but not by <jats:styled-content style="fixed-case">B</jats:styled-content> or <jats:styled-content style="fixed-case">T</jats:styled-content> cells and characterized by a different and faster intracellular routing, leads to enhanced <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell activation.</jats:p>
Journal
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- European Journal of Immunology
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European Journal of Immunology 43 (10), 2554-2565, 2013-08-05
Wiley
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Details 詳細情報について
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- CRID
- 1361418519340265472
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- ISSN
- 15214141
- 00142980
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- Data Source
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- Crossref