title: Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells.
abstract: 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.
authors.affiliation: State Key Laboratory for Agro-Biotechnology China Agricultural University, Beijing 100193, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Youmin
authors.initials: Y
authors.lastname: Kang
authors.forename: George
authors.initials: G
authors.lastname: Pavlakis
authors.forename: Huali
authors.initials: H
authors.lastname: Jin
authors.forename: Jinyao
authors.initials: J
authors.lastname: Li
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Hu
authors.forename: Weibin
authors.initials: W
authors.lastname: Hu
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology / Q000378:metabolism; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000628:therapy; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019476:Insect Proteins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D012471:Salivary Proteins and Peptides / Q000276:immunology / Q000378:metabolism; D005423:Siphonaptera / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019444:Vaccines, DNA
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D015703:Antigens, CD; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D019476:Insect Proteins; D012471:Salivary Proteins and Peptides; D019444:Vaccines, DNA