Published online 25 November 2002 doi:10.1084/jem.20020493
© Rockefeller University Press, 0022-1007/2002/12/1435/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 11, December 2, 2002 1435-1446
Complex Carbohydrates Are Not Removed During Processing of Glycoproteins by Dendritic Cells
:
Processing of Tumor Antigen MUC1 Glycopeptides for Presentation to Major Histocompatibility Complex Class IIrestricted T Cells
Anda M. Vlad1,
Stefan Muller2,
Mare Cudic3,
Hans Paulsen4,
Laszlo Otvos, Jr.3,
Franz-Georg Hanisch2 and
Olivera J. Finn1
1 Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
2 Institute of Biochemistry II, Medical Faculty of the University of Cologne, 50931 Cologne, Germany
3 The Wistar Institute, Philadelphia, PA 19104
4 Institute of Organic Chemistry, University of Hamburg, 20146 Hamburg, Germany
Address correspondence to Olivera J. Finn, University of Pittsburgh School of Medicine, Dept. of Immunology, W1142 Biomedical Science Tower, Terrace & DeSoto Sts., Pittsburgh, PA 15261. Phone: 412-648-9816; Fax: 412-648-7042; E-mail: ojfinn{at}pitt.edu
In contrast to protein antigens, processing of glycoproteins by dendritic cells (DCs) for presentation to T cells has not been well studied. We developed mouse T cell hybridomas to study processing and presentation of the tumor antigen MUC1 as a model glycoprotein. MUC1 is expressed on the surface as well as secreted by human adenocarcinomas. Circulating soluble MUC1 is available for uptake, processing, and presentation by DCs in vivo and better understanding of how that process functions in the case of glycosylated antigens may shed light on antitumor immune responses that could be initiated against this glycoprotein. We show that DCs endocytose MUC1 glycopeptides, transport them to acidic compartments, process them into smaller peptides, and present them on major histocompatability complex (MHC) class II molecules without removing the carbohydrates. Glycopeptides that are presented on DCs are recognized by T cells. This suggests that a much broader repertoire of T cells could be elicited against MUC1 and other glycoproteins than expected based only on their peptide sequences.
Key Words: antigen presenting cells endocytosis peptide epitopes glycoepitopes T cell hybridomas

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