DNA vaccine using invariant chain gene for delivery of CD4+ T cell epitope peptide derived from Japanese cedar pollen allergen inhibits allergen-specific IgE response.
To establish a new immunotherapy for type I allergic diseases without allergic side effects, we attempted to develop a DNA vaccine encoding both a CD4+ T cell epitope site in a major Japanese cedar pollen allergen (Cry j 2) and an invariant chain (Ii) for the delivery of the epitope peptide into the MHC class II loading pathway. We constructed a plasmid DNA encoding the Ii mutant either by replacement of the core CLIP (class II-associated invariant chain peptide) with a peptide corresponding to the major Cry j 2 CD4+ T cell epitope in BALB/c mice, designated as p247-258 (pCPCJ2), or by fusion of the Ii with p247-258 at the C terminus (pIiCJ2). As expected, repeated inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 induced no antibody response to Cry j 2. In contrast, intramuscular inoculation of BALB/c mice with pCPCJ2 or pIiCJ2 predominantly induced p247-258-specific Th1 cells, resulting in the inhibition of IgE response to subsequent Cry j 2 injections. Our results demonstrated that the plasmid DNA encoding the CD4+ T cell epitope and Ii can induce epitope-specific CD4+ T cell responses in vivo and the potential to regulate type I allergic reaction without allergic side effects.
Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
Masako
M
Toda
Michiyuki
M
Kasai
Hiroyuki
H
Hosokawa
Naoko
N
Nakano
Yoshifumi
Y
Taniguchi
Sakae
S
Inouye
Shuichi
S
Kaminogawa
Toshitada
T
Takemori
Masahiro
M
Sakaguchi
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D028203:Cedrus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011058:Pollen / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D000485:Allergens; D000944:Antigens, Differentiation, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D019444:Vaccines, DNA; C045084:invariant chain; D007073:Immunoglobulin E