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 (GalNAcA1-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.

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 / Napoletano, Chiara; Rughetti, Aurelia; AGERVIG TARP, Mp; Coleman, J; Bennett, Ep; Picco, G; Sale, Patrizio; DENDA NAGAI, K; Irimura, T; Mandel, U; Clausen, H; Frati, Luigi; TAYLOR PAPADIMITRIOU, J; Burchell, J; Nuti, Marianna. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 67:(2007), pp. 8358-8367. [10.1158/0008-5472.CAN-07-1035]

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.

NAPOLETANO, Chiara;RUGHETTI, Aurelia;SALE, PATRIZIO;FRATI, Luigi;NUTI, Marianna
2007

Abstract

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 (GalNAcA1-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.
2007
MGL; C-type lectin; Dendritic Cells
01 Pubblicazione su rivista::01a Articolo in rivista
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 / Napoletano, Chiara; Rughetti, Aurelia; AGERVIG TARP, Mp; Coleman, J; Bennett, Ep; Picco, G; Sale, Patrizio; DENDA NAGAI, K; Irimura, T; Mandel, U; Clausen, H; Frati, Luigi; TAYLOR PAPADIMITRIOU, J; Burchell, J; Nuti, Marianna. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 67:(2007), pp. 8358-8367. [10.1158/0008-5472.CAN-07-1035]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/366121
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