Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens

被引:65
作者
Hirahara, K
Tatsuta, T
Takatori, T
Ohtsuki, M
Kirinaka, H
Kawaguchi, J
Serizawa, N
Taniguchi, Y
Saito, S
Sakaguchi, M
Inouye, S
Shiraishi, A
机构
[1] Sankyo Co Ltd, Neurosci & Immunol Res Labs, Shinagawa Ku, Tokyo 1408710, Japan
[2] Hayashibara Biochem Labs Inc, Okayama, Japan
[3] Jikei Univ, Sch Med, Tokyo, Japan
[4] Natl Inst Infect Dis, Tokyo, Japan
关键词
Japanese cedar pollen; allergen; Cry j 1; Cry j 2; peptide; T-cell determinant; epitope; immunotherapy; IgE;
D O I
10.1067/mai.2001.115481
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Peptide immunotherapy is a new approach to treating allergic diseases, but a therapeutic peptide for Japanese cedar pollinosis has not yet been developed. Objective: The aim or this study is to prepare and preclinically evaluate a hybrid peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens. Methods: The recombinant hybrid peptide was prepared after immunodominance of 7 T-cell determinants was confirmed by means of PBMC proliferation assay in 113 volunteers with pollinosis. The hybrid peptide was compared with a mixture of the 7 T-cell determinants in a dose-dependent PBMC proliferation assay in 6 volunteers with pollinosis. PBMC proliferation and binding activity of serum IgE antibody against the hybrid peptide, Cry j 1, and Cry j 2 were investigated in 48 volunteers with pollinosis. Results: The hybrid peptide induced T-cell proliferation with an average 100-fold lower concentration than a mixture of the 7 peptides. PBMCs from 44 (92 %) of 48 volunteers proliferated against the hybrid peptide, with significant correlation (r = 0.87) in T-cell proliferation against Cry j 1 and Cry j 2. No serum IgE antibodies specific to Cry j 1 or Cry j 2 bound to the hybrid peptide. Conclusion: A hybrid peptide comprising 7 T-cell determinants has the potential for inducing T-cell proliferative responses that is superior to the potential of a mixture of the T-cell determinants and comparable with that of Cry j 1 and Cry j 2. The hybrid peptide will be of use in specific immunotherapy against Japanese cedar pollinosis.
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收藏
页码:94 / 100
页数:7
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