Linked Life Data

19007994

Source:http://linkedlifedata.com/resource/pubmed/id/19007994

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-11-3
pubmed:abstractText
The MUC1 glycoprotein is considered a tumor antigen due to its over expression and aberrant glycosylation in cancer tissues. The latter results in appearance of new antigenic tumor specific glycopeptides not found on normal glycoforms of the mucin. MUC1 glycopeptides can be presented by APCs on MHC class II molecules to activate glycopeptide specific helper T-cells. No study has yet reported presentation of MUC1 glycopeptides on MHC class I molecules as stimulators of cytotoxic T-cells. In this study we show that human immunoproteasomes and cathepsin-L can generate octa to undecameric glycopeptides from the MUC1 repeat domain in vitro. We identified glycosylated fragments of which the decameric glycopeptide SAP10 [SAPDT(GalNAc)RPAPG] containing a single sugar binds with comparable strength to the MHC class I allele HLA A*0201 as predicted high-score binding epitopes of the tandem repeat. The same sequence glycosylated with the disaccharide Gal-GalNAc does not bind. The glycan on SAP10 is predicted by molecular modeling to either protrude out or point into the MHC groove. SAPDTRPAPG peptide and the respective glycopeptide stimulated cytotoxic T-cells in vitro. Our findings suggest that MUC1 tandem repeat glycopeptides are capable of activating both helper and cytotoxic T-cells and thus represent good candidates for further development as vaccines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1872-9142
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-40
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Identification of O-glycosylated decapeptides within the MUC1 repeat domain as potential MHC class I (A2) binding epitopes.
pubmed:affiliation
Center of Biochemistry, Medical Faculty, and Center for Molecular Medicine Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural