Epitope located N-glycans impair the MHC-I epitope generation and presentation.

Details

Serval ID
serval:BIB_46F3C01EE137
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Epitope located N-glycans impair the MHC-I epitope generation and presentation.
Journal
Electrophoresis
Author(s)
Chiritoiu G.N., Jandus C., Munteanu C.V., Ghenea S., Gannon P.O., Romero P., Petrescu S.M.
ISSN
1522-2683 (Electronic)
ISSN-L
0173-0835
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
37
Number
11
Pages
1448-1460
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
The degradation process of the antigens specific to MHC-I presentation depends mainly on the proteasomal proteases in the cytosol. However, since many antigens are glycoproteins, including tumor antigens or viruses envelope proteins, their glycosylation status could also affect their processing and presentation. Here, we investigate the processing of tyrosinase, a multiple glycosylated tumor antigen overexpressed in human malignant melanoma. By LC-MS/MS analysis of human tyrosinase expressed in a melanoma cell, we show that all seven sites of tyrosinase are at least partially N-glycosylated. Using human CD8+ T-cell clones specific for the tyrosinase epitope YMDGTMSQV (369-377), including an N-glycosylation site, we found that transfectants of single and triple N-glycosylation mutants are recognized by specific T cells. Importantly, single, triple, and the aglycosylated tyrosinase mutants lacking the epitope located N-glycosylation site (N371D) were able to trigger higher CD8+ T-cell activation. The LC/MS analysis showed significant increase of the amount of YMDGTMSQV peptide resulted from accelerated oligomerization and degradation of aglycosylated mutants. The generation of the antigenic peptide by the antigen processing machinery is therefore largely independent of tyrosinase N-glycosylation. However, while distal N-glycans had no effect on the epitope generation, the mutants lacking the N371 glycan generated the antigenic peptide more efficiently. We conclude that epitope located N-glycans limit the ability of human tyrosinase to provide HLA-A2-restricted antigen for recognition by specific CD8+ T cells.
Pubmed
Web of science
Create date
31/07/2016 12:00
Last modification date
20/08/2019 14:52
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