Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation

European Journal of Immunology
Rodney A RosaliaCornelis J M Melief

Abstract

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T-cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre-)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte-derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome- and transporter associated with Ag processing-dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and ...Continue Reading

References

Apr 1, 1998·Nature·J Banchereau, R M Steinman
Dec 8, 1998·The Journal of Experimental Medicine·S R BennettW R Heath
Mar 13, 2001·Annual Review of Immunology·M K JenkinsK A Pape
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danita H SchuurhuisFerry Ossendorp
Feb 28, 2002·Annual Review of Immunology·Pierre GuermonprezSebastian Amigorena
Jun 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sander ZwavelingCornelis J M Melief
Oct 9, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Masakuni HoriguchiHiroyuki Arai
Dec 12, 2003·Nature Reviews. Immunology·Ulrich H von Andrian, Thorsten R Mempel
Feb 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Djordje AtanackovicSacha Gnjatic
Mar 17, 2004·The Journal of Experimental Medicine·Laura C BonifazRalph M Steinman
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martijn S BijkerSjoerd H van der Burg
Nov 1, 2007·European Journal of Immunology·Ian H FrazerJohn T Schiller
Jan 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gemma G KenterCornelis J M Melief
Apr 4, 2008·Immunology Letters·Suzanne F G van HeldenCarl G Figdor
Apr 5, 2008·European Journal of Immunology·Vania ManolovaMartin F Bachmann
Apr 18, 2008·Nature Reviews. Cancer·Cornelis J M Melief, Sjoerd H van der Burg
Sep 19, 2008·Immunity·Cornelis J M Melief
Jan 9, 2009·European Journal of Immunology·Florence FaureSebastian Amigorena
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Frank M SpeetjensSjoerd H van der Burg
Apr 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Nadine van MontfoortFerry Ossendorp
Jun 13, 2009·Journal of Immunological Methods·Lichen JingDavid M Koelle
Nov 6, 2009·The New England Journal of Medicine·Gemma G KenterCornelis J M Melief
Nov 27, 2009·BMC Bioinformatics·Valentina BaldazziFilippo Castiglione
Dec 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kenneth L RockLianjun Shen
Mar 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sven BurgdorfChristian Kurts
Apr 28, 2010·Annual Review of Microbiology·John T Schiller, Douglas R Lowy
Jun 12, 2010·Science·Reshma Singh, Peter Cresswell
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marij J P WeltersSjoerd H van der Burg
Jan 18, 2011·Current Opinion in Immunology·Sjoerd H van der Burg, Cornelis J M Melief
Jan 25, 2011·Current Opinion in Immunology·Li-Min HuangDing-Shinn Chen
Jul 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brendon Y ChuaDavid C Jackson

❮ Previous
Next ❯

Citations

Jul 30, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Luis J CruzFerry Ossendorp
Feb 16, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Eleni Maria VarypatakiWim Jiskoot
Aug 5, 2015·Biochimica Et Biophysica Acta·Eran OphirLana E Kandalaft
May 17, 2015·Molecular Immunology·Sebastien ApcherRobin Fåhraeus
Feb 11, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sima RahimianFerry Ossendorp
Mar 31, 2015·Immunology·Thomas NiezoldMatthias Tenbusch
Jul 28, 2015·The Journal of Clinical Investigation·Cornelis J M MeliefSjoerd H van der Burg
Apr 15, 2016·Science Translational Medicine·Pedro RomeroGeorge Coukos
Mar 19, 2015·Frontiers in Immunology·Gabriela Andrea Pizzurro, María Marcela Barrio
Jun 21, 2016·Immunological Reviews·Peter van Endert
Jul 6, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elodie BelnoueMadiha Derouazi
Jan 10, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patricia M Santos, Lisa H Butterfield
Dec 11, 2014·World Journal of Clinical Oncology·Ricardo Rosales, Carlos Rosales
May 13, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erika A K FletcherSara M Mangsbo
Jul 24, 2015·Clinical and Vaccine Immunology : CVI·Mariateresa CoppolaAnnemieke Geluk
Feb 26, 2019·Melanoma Research·Deena M MaurerLazar Vujanovic
Feb 26, 2016·Scientific Reports·Ilse DingjanGeert van den Bogaart
Nov 10, 2018·Anti-cancer Agents in Medicinal Chemistry·Hanjiao QinZhuo Zhang
Feb 15, 2019·Science Translational Medicine·Sunil SinghalEvgeniy B Eruslanov
Jul 31, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexandre E NowillPedro O de Campos-Lima
Jan 16, 2020·The Journal of Experimental Medicine·Aude-Hélène CapiettoLélia Delamarre
Jan 23, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenbin MaBenoît J Van den Eynde
Feb 1, 2016·Chemical Science·Mariusz Skwarczynski, Istvan Toth
May 15, 2018·Frontiers in Immunology·Brett J HosFerry Ossendorp
Jul 13, 2018·Therapeutic Advances in Vaccines and Immunotherapy·Victoria A BrentvilleLindy G Durrant
Feb 7, 2018·Frontiers in Immunology·Alex RubinsteynJeffrey Hammerbacher
Mar 14, 2019·Frontiers in Immunology·Natalia K BotelhoPedro Romero
Feb 19, 2019·NPJ Vaccines·Robert E Hollingsworth, Kathrin Jansen
Jun 21, 2020·Journal for Immunotherapy of Cancer·Victoria A BrentvilleLindy G Durrant
Nov 27, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna LissinaVictor Appay

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Landau-Kleffner Syndrome

Landau Kleffner syndrome (LKS), also called infantile acquired aphasia, acquired epileptic aphasia, or aphasia with convulsive disorder, is a rare childhood neurological syndrome characterized by the sudden or gradual development of aphasia (the inability to understand or express language) and an abnormal electroencephalogram. Discover the latest research on LKS here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.