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Efficient Induction of CD25(-) iTreg by Co-Immunization Requires Strongly Antigenic Epitopes for T Cells

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posted on 21.03.2012, 00:00 by Shuang Geng, Yang Yu, Youmin Kang, George Pavlakis, Huali Jin, Jinyao Li, Yanxin Hu, Weibin Hu, Shuang Wang, Bin Wang
Background: We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40(low) IL-10(high) tolerogenic DCs, which in turn stimulates the expansion of antigenspecific CD4(+)CD25(-)Foxp3(+) regulatory T cells (CD25(-) iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25(-) iTreg induction. Results: In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25(-) iTreg induction. Firstly, we showed that the induction of CD25(-) iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25(-) iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25(-) iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. Conclusions: Our data thus indicate that efficient induction of CD25- iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25- iTreg for clinical applications such as flea allergic dermatitis.


This work was supported in part by the National Nature Science Foundation of China (20771602 and 30930068) and State Key Lab Innovative Research initiation (2008SKLAB05-02) to BW.


Publisher Statement

© 2011 Geng et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/license/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The original version is available through BioMed Central at DOI: 10.1186/1471-2172-12-27.


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