Retention of immunogenicity produced by mucin1 peptides with glycosylation site substitutions

Abstract

Mucin1 (MUC1) with altered glycosylation behaves as an antigen unique to adenocarcinomas (ADCs). As a step toward DNA vaccines, the goal of this work was to determine whether MUC1 peptides substituted with an asparagine at O-linked glycosylation sites, might expose MUC1 peptide backbone to serve as immunogens to generate cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells of patients with ADCs. Substitution of some or all tyrosine and serine residues by asparagine in MUC1 did not inhibit the generation of mucin-specific CTLs. This suggests that MUC1 tandem repeat altered sequences to prevent O-linked glycosylation may be useful as DNA vaccines with tumor specificity.

Keywords::

• Immunogenicity
• glycosylation site
• substitutions
• CTL
• MUC1

Acknowledgements

The authors are grateful to those mentioned in the text for supplying materials, Glenda Ramsey, Baptist-St. Anthony’s HSC, Harrington Cancer Center Cell Processing Laboratory, Amarillo, TX for peripheral blood mononuclear cells, and to Melissa A. Braunger, Zhenyao Wang, Jeremiah Bresnahan, and Candace Myers for their editorial assistance.

Declaration of interest

This work was supported in part by the Department of Veterans Affairs Medical Research funds (S.E.W., K.E.D., and S.E.W.), the Department of the Army Career Development Award grant DAMD17-94-J-4161 (K.E.D.), and the Department of the Army Grant DAMD17-94-J-4272 (K.E.D. and S.E.W.). The authors report no declarations of interest.