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.
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 of 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.


CONCLUSIONS
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.
Hirahara
K
K
Sankyo Co, Ltd, Tokyo; Hayashibara Biochemical Laboratories, Inc, Okayama, Japan.
Tatsuta
T
T
Takatori
T
T
Ohtsuki
M
M
Kirinaka
H
H
Kawaguchi
J
J
Serizawa
N
N
Taniguchi
Y
Y
Saito
S
S
Sakaguchi
M
M
Inouye
S
S
Shiraishi
A
A
D000328:Adult; D000485:Allergens / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D004353:Drug Evaluation, Preclinical; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology*; D011058:Pollen / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014197:Trees / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; C065290:Cry j I protein, Cryptomeria japonica; C065291:Cry j II protein, Cryptomeria japonica; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E