Identification of EphB6 variant-derived epitope peptides recognized by cytotoxic T-lymphocytes from HLA-A24+ malignant glioma patients.
We found previously that EphB6, a member of the erythropoietin-producing hepatocyte (Eph) receptor tyrosine kinase family, was preferentially expressed in malignant gliomas. In the present study, RT-PCR revealed a putative secretory variant form of human EphB6 that was expressed in the majority of glioma cell lines, though not in normal tissues. The variant has a unique 54 amino acid sequence that is not found in the normal EphB6. Therefore, we attempted to determine the antigenic peptides unique to the variant for immunotherapy. The two variant-derived peptides had the ability to bind to HLA-A2402 molecules and each of them could induce cytotoxic T-lymphocytes (CTLs) in vitro in peripheral blood mononuclear cells of HLA-A24(+) glioma patients. Furthermore, the cytotoxicity was mediated by peptide-specific CD8(+) T cells in an HLA-A24 restricted manner. Taken together, the two peptides derived from the variant of EphB6 might be appropriate targets for peptide-based specific immunotherapy to HLA-A24(+) patients with malignant glioma.
Jin
Mingyue
M
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Fukuoka 830-0011, Japan.
Komohara
Yoshihiro
Y
Shichijo
Shigeki
S
Harada
Mamoru
M
Yamanaka
Ryuya
R
Miyamoto
Shigeaki
S
Nikawa
Junichi
J
Itoh
Kyogo
K
Yamada
Akira
A
D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry*; D005786:Gene Expression Regulation; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D015234:HLA-A Antigens / Q000737:chemistry*; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D036261:Receptor, EphB6 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*
D018076:DNA, Complementary; D000939:Epitopes; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D010455:Peptides; D036261:Receptor, EphB6