Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells
Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells
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DOI：
10.1186/1471-2172-12-27
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发表时间：
2011-05-05
期刊：
影响因子：
3
通讯作者：
Wang, Bin
中科院分区：
文献类型：
--
作者：
Geng, Shuang;Yu, Yang;Wang, Bin
背景：我们之前发现，与蛋白质抗原和编码相同抗原的DNA疫苗共同免疫可诱导CD40（低）IL-10（高）耐受性dc，这反过来刺激抗原特异性CD4(+) CD25- foxp3（+）调节性T细胞（CD25(-) iTreg）的扩增。然而，目前尚不清楚如何选择抗原序列来最大化耐受性抗原呈递，从而最大化CD25(-) iTreg诱导。结果：在本研究中，我们证明了CD25(-) iTreg诱导需要高抗原表位。首先，我们发现耐受性DC对CD25(-) iTreg的诱导可以被抗mhc - ii抗体阻断。接下来，CD25(-) iTreg的数量和抑制活性与表位激活T细胞的显性抗原性呈正相关。最后，在皮炎小鼠模型中，来自跳蚤过敏原的高抗原表位不仅诱导了更多的CD25(-) iTreg，而且比弱抗原表位更有效地阻止了对过敏原的过敏反应。结论：我们的数据表明，CD25(-) iTreg的有效诱导需要高抗原肽表位。这一发现表明，高抗原表位应该用于有效诱导CD25(-) iTreg，用于跳蚤过敏性皮炎等临床应用。
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 antigen-specific 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.