Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cancer Research |
| Vol/bind | 67 |
| Udgave nummer | 17 |
| Sider (fra-til) | 8358-67 |
| Antal sider | 9 |
| ISSN | 0008-5472 |
| DOI | |
| Status | Udgivet - 2007 |
Bibliografisk note
Keywords: Antigens, Tumor-Associated, Carbohydrate; Cells, Cultured; Dendritic Cells; Endocytosis; Glycosylation; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; K562 Cells; Lectins, C-Type; Mucin-1; Protein Isoforms; Recombinant ProteinsAdgang til dokumentet
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I: Cancer Research, Bind 67, Nr. 17, 2007, s. 8358-67.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells
AU - Napoletano, Chiara
AU - Rughetti, Aurelia
AU - Agervig Tarp, Mads P
AU - Coleman, Julia
AU - Bennett, Eric P
AU - Picco, Gianfranco
AU - Sale, Patrizio
AU - Denda-Nagai, Kaori
AU - Irimura, Tatsuro
AU - Mandel, Ulla
AU - Clausen, Henrik
AU - Frati, Luigi
AU - Taylor-Papadimitriou, Joyce
AU - Burchell, Joy
AU - Nuti, Marianna
N1 - Keywords: Antigens, Tumor-Associated, Carbohydrate; Cells, Cultured; Dendritic Cells; Endocytosis; Glycosylation; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; K562 Cells; Lectins, C-Type; Mucin-1; Protein Isoforms; Recombinant Proteins
PY - 2007
Y1 - 2007
N2 - The type of interaction between tumor-associated antigens and specialized antigen-presenting cells such as dendritic cells (DCs) is critical for the type of immunity that will be generated. MUC1, a highly O-glycosylated mucin, is overexpressed and aberrantly glycosylated in several tumor histotypes. This results in the expression of tumor-associated glycoforms and in MUC1 carrying the tumor-specific glycan Tn (GalNAcalpha1-O-Ser/Thr). Glycopeptides corresponding to three tandem repeats of MUC1, enzymatically glycosylated with 9 or 15 mol of GalNAc, were shown to specifically bind and to be internalized by immature monocyte-derived DCs (iDCs). Binding required calcium and the GalNAc residue and was competed out by GalNAc polymer and Tn-MUC1 or Tn-MUC2 glycopeptides. The macrophage galactose-type C-type lectin (MGL) receptor expressed on iDCs was shown to be responsible for the binding. Confocal analysis and ELISA done on subcellular fractions of iDCs showed that the Tn-MUC1 glycopeptides colocalized with HLA class I and II compartments after internalization. Importantly, although Tn-MUC1 recombinant protein was bound and internalized by MGL, the glycoprotein entered the HLA class II compartment, but not the HLA class I pathway. These data indicate that MGL expressed on iDCs is an optimal receptor for the internalization of short GalNAcs carrying immunogens to be delivered into HLA class I and II compartments. Such glycopeptides therefore represent a new way of targeting the HLA class I and II pathways of DCs. These results have possible implications in designing cancer vaccines.
AB - The type of interaction between tumor-associated antigens and specialized antigen-presenting cells such as dendritic cells (DCs) is critical for the type of immunity that will be generated. MUC1, a highly O-glycosylated mucin, is overexpressed and aberrantly glycosylated in several tumor histotypes. This results in the expression of tumor-associated glycoforms and in MUC1 carrying the tumor-specific glycan Tn (GalNAcalpha1-O-Ser/Thr). Glycopeptides corresponding to three tandem repeats of MUC1, enzymatically glycosylated with 9 or 15 mol of GalNAc, were shown to specifically bind and to be internalized by immature monocyte-derived DCs (iDCs). Binding required calcium and the GalNAc residue and was competed out by GalNAc polymer and Tn-MUC1 or Tn-MUC2 glycopeptides. The macrophage galactose-type C-type lectin (MGL) receptor expressed on iDCs was shown to be responsible for the binding. Confocal analysis and ELISA done on subcellular fractions of iDCs showed that the Tn-MUC1 glycopeptides colocalized with HLA class I and II compartments after internalization. Importantly, although Tn-MUC1 recombinant protein was bound and internalized by MGL, the glycoprotein entered the HLA class II compartment, but not the HLA class I pathway. These data indicate that MGL expressed on iDCs is an optimal receptor for the internalization of short GalNAcs carrying immunogens to be delivered into HLA class I and II compartments. Such glycopeptides therefore represent a new way of targeting the HLA class I and II pathways of DCs. These results have possible implications in designing cancer vaccines.
U2 - 10.1158/0008-5472.CAN-07-1035
DO - 10.1158/0008-5472.CAN-07-1035
M3 - Journal article
C2 - 17804752
SN - 0008-5472
VL - 67
SP - 8358
EP - 8367
JO - Cancer Research
JF - Cancer Research
IS - 17
ER -