Binding of tumor antigen mucin (MUC1) derived peptides to the heat shock protein DnaK

Item Type:	Article
Title:	Binding of tumor antigen mucin (MUC1) derived peptides to the heat shock protein DnaK
Creators Name:	Schreiber, J. and Stahn, R. and Schenk, J.A. and Karsten, U. and Pecher, G.
Abstract:	The human epithelial mucin encoded by the gene MUC1 is a tumor-associated antigen expressed on breast, pancreatic, colon and ovarian cancer cells recognized by cytotoxic T-cells and antibodies. Underglycosylated as well as glycosylated mucin-peptide epitopes are promising targets for vaccination against cancer. Heat shock proteins of 70 kDa (HSP70), also highly expressed in tumor cells, can function as chaperones for peptides and proteins and are involved in antigen processing. The involvement of HSP70 molecules in mucin antigen binding, processing and presentation has not yet been examined. Here we present first results concerning the relative binding affinities of various mucin- derived peptides to the bacterial 70 kDa heat shock protein DnaK. Interestingly, longer mucin peptides reveal a higher affinity to DnaK than short peptides. The non-glycosylated mucin-derived peptides of 5-8 amino acids length were able to compete with a high affinity (unrelated) reference peptide at millimolar concentrations. Glycosylation of the investigated short peptides lowers their binding affinity to DnaK, depending on the position of the carbohydrate. The binding affinity is not influenced by free charges at unprotected ends. The peptide (MUC1)5 consisting of five repeating units has an affinity enhanced by a factor of three as compared to the peptide with only one repeating unit. Mucin-peptide-HSP-complexes could be the basis of developing new kinds of tumor vaccines.
Keywords:	DnaK, Glycosylation and Binding Affinity, HSP70, MUC1, Peptide Antigens
Source:	Anticancer Research
ISSN:	0250-7005
Publisher:	Delinassios
Volume:	20
Number:	5A
Page Range:	3093-3098
Date:	1 September 2000
PubMed:	View item in PubMed

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