Enhanced cross-presentation and improved CD8+ T cell responses after mannosylation of synthetic long peptides in mice

PloS One
Judith RauenSven Burgdorf

Abstract

The use of synthetic long peptides (SLP) has been proven to be a promising approach to induce adaptive immune responses in vaccination strategies. Here, we analyzed whether the efficiency to activate cytotoxic T cells by SLP-based vaccinations can be increased by conjugating SLPs to mannose residues. We could demonstrate that mannosylation of SLPs results in increased internalization by the mannose receptor (MR) on murine antigen-presenting cells. MR-mediated internalization targeted the mannosylated SLPs into early endosomes, from where they were cross-presented very efficiently compared to non-mannosylated SLPs. The influence of SLP mannosylation was specific for cross-presentation, as no influence on MHC II-restricted presentation was observed. Additionally, we showed that vaccination of mice with mannosylated SLPs containing epitopes from either ovalbumin or HPV E7 resulted in enhanced proliferation and activation of antigen-specific CD8+ T cells. These findings demonstrate that mannosylation of SLPs augments the induction of a cytotoxic T cell response in vitro and in vivo and might be a promising approach to induce cytotoxic T cell responses in e.g. cancer therapy and anti-viral immunity.

References

Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·R E ToesW M Kast
Jun 1, 1996·Vaccine·V ApostolopoulosI F McKenzie
Dec 1, 1996·The Journal of Allergy and Clinical Immunology·M SakaguchiS Inouye
Nov 5, 1999·International Immunology·R JordensF Koning
Jun 1, 2000·Journal of the American Society for Mass Spectrometry·D J HarveyI B Wilson
Jul 18, 2000·European Journal of Immunology·V ApostolopoulosI F McKenzie
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anneke EngeringYvette van Kooyk
Jun 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sander ZwavelingCornelis J M Melief
Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcello ChieppaPaola Allavena
Aug 12, 2004·Blood·Jurgen HerreGordon D Brown
Dec 2, 2004·Expert Opinion on Biological Therapy·Tibor KelerMichael W Fanger
Feb 16, 2005·Journal of Neuroimmunology·Mariken E LucaLex Nagelkerken
May 3, 2006·Experimental Cell Research·Marisa J WainszelbaumM Alejandro Barbieri
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sven BurgdorfChristian Kurts
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emma J McKenzieLuisa Martinez-Pomares
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li-Zhen HeRaphael Clynes
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martijn S BijkerSjoerd H van der Burg
Oct 25, 2007·International Journal of Cancer. Journal International Du Cancer·Corlien A AarnoudseYvette van Kooyk
Feb 7, 2008·Cancer Immunology, Immunotherapy : CII·Hyun-Il ChoEsteban Celis
Apr 18, 2008·Nature Reviews. Cancer·Cornelis J M Melief, Sjoerd H van der Burg
Jan 9, 2009·European Journal of Immunology·Florence FaureSebastian Amigorena
Apr 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Nadine van MontfoortFerry Ossendorp
Nov 6, 2009·The New England Journal of Medicine·Gemma G KenterCornelis J M Melief
Jun 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Matthias ZehnerSven Burgdorf
Jun 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claire Mary SmithPeter William Andrew
Sep 2, 2011·Microbial Biotechnology·Ennio De Gregorio, Rino Rappuoli
Mar 28, 2012·Advances in Immunology·Thorbald van Hall, Sjoerd H van der Burg
Mar 28, 2012·Advances in Immunology·Gijs G P ZomFerry Ossendorp
Aug 24, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Suzanne van DuikerenRamon Arens
May 28, 2013·Seminars in Immunology·Ramon ArensCornelis J M Melief

❮ Previous
Next ❯

Citations

May 17, 2015·Molecular Immunology·Sebastien ApcherRobin Fåhraeus
Oct 7, 2015·Frontiers in Immunology·Sachiko Hirosue, Juan Dubrot
Jan 26, 2018·Viral Immunology·Brendon Y ChuaDavid C Jackson
Mar 1, 2018·Annual Review of Immunology·J Magarian Blander
May 15, 2018·Frontiers in Immunology·Brett J HosFerry Ossendorp
Oct 12, 2016·Nanobiomedicine·Tatiana LyalinaElena Svirshchevskaya
Apr 11, 2019·Macromolecular Bioscience·Stefan KramerRudolf Zentel
Dec 9, 2020·Molecular & Cellular Proteomics : MCP·Annika NeldeJuliane Sarah Walz
Feb 16, 2021·Molecular & Cellular Proteomics : MCP·Annika NeldeJuliane S Walz
Mar 23, 2021·The FEBS Journal·Marko AnderluhSandra J van Vliet

❮ Previous
Next ❯

Methods Mentioned

BETA
reversed phase chromatography
flow cytometry
FCS

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.