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Glycobiology Advance Access published online on October 18, 2006
Glycobiology, doi:10.1093/glycob/cwl061
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 22, 2006
Revised October 5, 2006
Accepted October 15, 2006

Article

Identification of a Novel Cancer-Specific Immunodominant Glycopeptide Epitope in the MUC1 Tandem Repeat

Mads A. Tarp 1, Anne Louise Sørensen 1, Ulla Mandel 1, Hans Paulsen 2, Joy Burchell 3, Joyce Taylor-Papadimitriou 3, and Henrik Clausen 1 *

1 Department of Cellular and Molecular Medicine & Department of Oral Diagnostics, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark
2 Department of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
3 Cancer Research UK, Breast Cancer Biology Group, King's College London, Thomas Guy House, Guy's Hospital, London SE1 9RT, UK

* To whom correspondence should be addressed.
Henrik Clausen, E-mail: hc{at}imbg.ku.dk


  Abstract

The cell membrane mucin MUC1 is over-expressed and aberrantly glycosylated in many cancers and cancer-associated MUC1 glycoforms represent potential targets for immunodiagnostic and therapeutic measures. We have recently shown that MUC1 with Tn and STn O-glycosylation are cancer-specific glycoforms, and that Tn/STn-MUC1 glycopeptide-based vaccines can override tolerance in human MUC1 transgenic mice and induce humoral immunity with high specificity for MUC1 cancer-specific glycoforms (Sorensen et al. 2006). In order to further characterize the immune response to Tn/STn-MUC1 glycoforms we generated monoclonal antibodies with specificity similar to the polyclonal antibody response found in transgenic mice. In the present study we define the immunodominant epitope on Tn/STn-MUC1 glycopeptides to the region including the amino acids GSTA of the MUC1 20-amino acid tandem repeat (HGVTSAPDTRPAPGSTAPPA). Most other MUC1 antibodies are directed to the PDTR region, although patients with antibodies to the GSTA region have been identified. A panel of other MUC1 glycoform-specific monoclonal antibodies was included for comparison. The study demonstrates that the GSTA region of the MUC1 tandem repeat contains a highly immunodominant epitope when presented with immature short O-glycans. The cancer-specific expression of this glycopeptide epitope makes it a prime candidate for immunodiagnostic and therapeutic measures.

Keywords: MUC1; monoclonal antibody; epitope mapping; O-glycosylation; cancer-specific.
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