T-cell epitope peptides
The T-cell epitope site on a Japanese cypress (hinoki) pollen allergen molecule has been identified by stimulating a T-cell line established from a patient suffering from Japanese cypress pollen allergy with an overlap peptide covering the primary structure of the Japanese cypress pollen allergen. The peptide is useful in peptide-based immunotherapy for patients with spring tree pollinosis including patients with Japanese cypress pollinosis having cross reactivity with Japanese cypress pollen. The peptide is also useful for diagnosing spring tree pollinosis.
1. A peptide derived from Japanese cypress pollen allergen Cha o 2, wherein the peptide consists of:
(i) (a) an amino acid sequence selected from the group consisting of SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80, said amino acid sequence having T-cell stimulating activity; or (1) (b) a fragment of an amino acid sequence selected from the set consisting of SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80, wherein each fragment has T-cell stimulating activity equivalent to that of the corresponding amino acid sequence of the set listed in (i) (b); or
(ii) a combination of sequences, the sequences being selected from the amino acid sequences listed in (i) (a) and the amino acid sequence fragments recited in (i) (b).
2. A composition comprising the peptide of claim 1 , as an active ingredient, and a pharmaceutically acceptable diluent or carrier.
3. The composition of claim 2 , wherein said composition can reduce the symptoms of Japanese cypress pollinosis or cedar pollinosis in a patient.
4. A peptide derived from Japanese cypress pollen allergen Cha o 2, wherein the peptide consists of a combination of two or more amino acid sequences and a linker sensitive to enzyme cleavage between each amino acid sequence, wherein said two or more amino acid sequences of the combination are:
sequences selected from the group consisting of SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80, the sequences having T-cell stimulating activity; or
fragments of sequences selected from the set consisting of SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80, each fragment having T-cell stimulating activity equivalent to that of the corresponding sequence.
5. The peptide of claim 4 , wherein said linker is Arg-Arg or Lys-Lys.
6. A composition comprising the peptide of claim 4 , as an active ingredient, and a pharmaceutically acceptable diluent or carrier.
7. The composition of claim 6 , wherein said composition can reduce the symptoms of Japanese cypress pollinosis or cedar pollinosis in a patient.
8. The peptide of claim 1 , wherein the peptide consists of:
(A) an amino acid sequence selected from sequences of the group consisting of: SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, and SEQ ID NO: 80; or
(B) a combination of amino acid sequences selected from the sequences listed in (A).
9. The peptide of claim 1 , wherein the peptide consists of:
(x) an amino acid sequence selected from sequences of the group consisting of SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, and SEQ ID NO: 80; or
(y) a combination of amino acid sequences selected from the sequences listed in (x).
10. The peptide of claim 1 , wherein the peptide consists of:
(X) an amino acid sequence selected from sequences of the group consisting of SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, and SEQ ID NO: 80; or
(Y) a combination of amino acid sequences selected from the sequences listed in (X).
11. A composition comprising the peptide of claim 8 as an active ingredient, and a pharmaceutically acceptable diluent or carrier.
12. A composition comprising the peptide of claim 9 as an active ingredient, and a pharmaceutically acceptable diluent or carrier.
13. A composition comprising the peptide of claim 10 as an active ingredient, and a pharmaceutically acceptable diluent or carrier.