Identification of cyclophilin B-derived peptides capable of inducing histocompatibility leukocyte antigen-A2-restricted and tumor-specific cytotoxic T lymphocytes.
We recently suggested that cyclophilin B (Cyp-B) is a tumor antigen recognized by histocompatibility leukocyte antigen (HLA)-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). In this study, we tried to identify Cyp-B-derived epitopes, which can induce HLA-A2-restricted and tumor-specific CTLs in cancer patients. The tumor-infiltrating lymphocytes (TILs) from an HLA-A0207 patient with colon cancer were found to respond to COS-7 cells when co-transfected with the Cyp-B gene and either HLA-A0201, -A0206, or -A0207 cDNA. These TILs contained CTLs capable of recognizing either the Cyp-B(129 - 138) or the Cyp-B(172 - 179) peptide among 28 different peptides, all of which were prepared based on the HLA-A2 binding motif. Both Cyp-B peptides possessed the ability to induce tumor-specific CTLs in HLA-A2(+) cancer patients. Cyp-B(172 - 180 (V)), which is a 9-mer peptide with valine added at the C terminus, showed no clear superiority over the parental Cyp-B(172 - 179) peptide in an in vitro sensitization experiment. In vitro-sensitized T cells with these peptides responded to cancer cells in an HLA-A2-restricted manner. These two Cyp-B peptides could be useful for specific immunotherapy of HLA-A2(+) cancer patients.
Tamura
M
M
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan. kyogo@med.kurume-u.ac.jp
Nishizaka
S
S
Maeda
Y
Y
Ito
M
M
Harashima
N
N
Harada
M
M
Shichijo
S
S
Itoh
K
K
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology; D021983:Cyclophilins / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000502:physiology; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D019696:Peptidylprolyl Isomerase; D013274:Stomach Neoplasms / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; C081786:cyclophilin B; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase