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.
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.
Vlad
Anda M
AM
Department of Immunology, University of Pittsburgh School of Medicine, Biomedical Science Tower, Terrace & DeSoto Streets, Pittsburgh, PA 15261, USA.
Muller
Stefan
S
Cudic
Mare
M
Paulsen
Hans
H
Otvos
Laszlo
L
Hanisch
Franz-Georg
FG
Finn
Olivera J
OJ
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000378:metabolism*; D004705:Endocytosis; D000939:Epitopes; D005260:Female; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D018396:Mucin-1