Original Article
Subject Category: Immunology/Infection
Journal of Investigative Dermatology (2005) 124, 125–131; doi:10.1111/j.0022-202X.2004.23515.x
Epitope-Specific Antibody Response to Mel-CAM Induced by Mimotope Immunization
Christine Hafner*, Stefan Wagner†, Joanna Jasinska†, Dorothee Allwardt†, Otto Scheiner†, Klaus Wolff*, Hubert Pehamberger*, Ursula Wiedermann† and Heimo Breiteneder†
- *Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Austria
- †Department of Pathophysiology, Division of Applied Experimental Pathology, Medical University of Vienna, Austria
Correspondence: Heimo Breitneder PhD, Department of Pathophysiology, Division of Applied Experimental Pathology, Medical University of Vienna, Waehringer, Guertel 18-20, A-1090, Vienna, Austria. Email: heimo.breitneder@meduniwien.ac.at
Received 14 April 2004; Revised 10 August 2004; Accepted 14 August 2004; Published online 21 December 2004.
Abstract
Peptide mimotopes of tumor antigen epitopes have been proposed as components of tumor vaccines. In this study, we determined the immunogenicity of melcam mim1 and melcam mim2, peptide mimics of an epitope of the melanoma cell-adhesion molecule (Mel-CAM). BALB/c mice were vaccinated either with mimotopes or mimotopes coupled to tetanus toxoid (TT). The antibody responses of mice to melcam mim1, melcam mim2, and recombinant Mel-CAM were analyzed by an ELISA and immunoblot analyses. TT-coupled mimotopes led to high titers of IgG mainly of the IgG2a subclass to melcam mim1 and melcam mim2. Immunization with each of the mimotope formulations induced antibodies that cross-reacted with recombinant Mel-CAM. Uncoupled mimotopes induced lymphocyte proliferation and cytokine production in spleen cell cultures indicating that both peptide mimotopes also contained T cell epitopes. TT-coupled mimotopes induced T helper (Th)1 (interleukin (IL)-2, interferon-
) and Th2 (IL-4, IL-5) cytokines, whereas uncoupled mimotopes induced a Th1-biased T cell response. Our results suggest that mimotopes potentially represent a novel vaccine approach to induce a tumor antigen-specific humoral and cellular response.
Keywords:
antibody response, melanoma, Mel-CAM, mimotope
Abbreviations:
IFN, interferon; IL, interleukin; mAb, monoclonal antibody; Mel-CAM, melanoma cell-adhesion molecule; Th1, T helper 1; TT, tetanus toxoid
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