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PMID: 12461079 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 II-restricted T cells.

The Journal of experimental medicine ·Vol. 196 ·No. 11 ·2002-12-02 ·Pages 1435-46

Vlad AM, Muller S, Cudic M, Paulsen H, Otvos L, Hanisch FG, Finn OJ

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Antigen Presentation Dendritic Cells/metabolism Endocytosis Epitopes Female Glycosylation Histocompatibility Antigens Class II/immunology Mice Mice, Inbred C57BL Molecular Sequence Data Mucin-1/chemistry,metabolism T-Lymphocytes/immunology
Chemicals
Epitopes Histocompatibility Antigens Class II Mucin-1
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Vlad Anda M
Department of Immunology, University of Pittsburgh School of Medicine, Biomedical Science Tower, Terrace & DeSoto Streets, Pittsburgh, PA 15261, USA.
Muller Stefan
Cudic Mare
Paulsen Hans
Otvos Laszlo
Hanisch Franz-Georg
Finn Olivera J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20020493
Published
2002-12-02
Pages
1435-46
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2194269
Subset
IM
Grants
NCI NIH HHS · R01 CA84106 · United States
NCI NIH HHS · P01 CA 73743 · United States
NCI NIH HHS · R01 CA 56103 · United States
NIGMS NIH HHS · GM 45011 · United States
NCI NIH HHS · P01 CA073743 · United States
NCI NIH HHS · R01 CA056103 · United States
NCI NIH HHS · R01 CA084106 · United States
External Links
PubMed source DOI: 10.1084/jem.20020493 PMC Full Text View journal details
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