Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.

Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and prese...

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Autores principales:	Caroline B Madsen, Cecilie Petersen, Kirstine Lavrsen, Mikkel Harndahl, Søren Buus, Henrik Clausen, Anders E Pedersen, Hans H Wandall
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d02991980215470ebc500f26e83a22fc
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spelling	oai:doaj.org-article:d02991980215470ebc500f26e83a22fc2021-11-18T08:07:35ZCancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.1932-620310.1371/journal.pone.0050139https://doaj.org/article/d02991980215470ebc500f26e83a22fc2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189185/?tool=EBIhttps://doaj.org/toc/1932-6203Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo response to a cancer related tumor antigen, Balb/c or B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/J (HLA-A2 transgenic) mice were immunized with a non-glycosylated or GalNAc-glycosylated MUC1 derived peptide followed by comparison of T cell proliferation, IFN-γ release, and antibody induction. GalNAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells.Caroline B MadsenCecilie PetersenKirstine LavrsenMikkel HarndahlSøren BuusHenrik ClausenAnders E PedersenHans H WandallPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50139 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Caroline B Madsen Cecilie Petersen Kirstine Lavrsen Mikkel Harndahl Søren Buus Henrik Clausen Anders E Pedersen Hans H Wandall Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.
description	Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo response to a cancer related tumor antigen, Balb/c or B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/J (HLA-A2 transgenic) mice were immunized with a non-glycosylated or GalNAc-glycosylated MUC1 derived peptide followed by comparison of T cell proliferation, IFN-γ release, and antibody induction. GalNAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells.
format	article
author	Caroline B Madsen Cecilie Petersen Kirstine Lavrsen Mikkel Harndahl Søren Buus Henrik Clausen Anders E Pedersen Hans H Wandall
author_facet	Caroline B Madsen Cecilie Petersen Kirstine Lavrsen Mikkel Harndahl Søren Buus Henrik Clausen Anders E Pedersen Hans H Wandall
author_sort	Caroline B Madsen
title	Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.
title_short	Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.
title_full	Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.
title_fullStr	Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.
title_full_unstemmed	Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.
title_sort	cancer associated aberrant protein o-glycosylation can modify antigen processing and immune response.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d02991980215470ebc500f26e83a22fc
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Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.

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