Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors.
Although specific immunotherapy is one candidate treatment of brain tumor, the molecular basis of T-cell-mediated recognition of brain tumors has not yet been elucidated. In this study, we tried to identify brain tumor antigens using HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs). As an HLA-A2-restricted OK-CTL line contained CTLs capable of responding to HLA-A2+ malignant glioma cells, this cell line was used for identification of brain tumor antigens. After screening a cDNA library from brain tumor cells, this CTL line was found to produce interferon (IFN)-gamma when cultured with COS-7 cells, which were cotransfected with both a cDNA clone (clone 1) and HLA-A0207 cDNA. Data base searches indicated that the clone 1 was 98% identical to that of the human ADP-ribosylation factor 4-like (ARF4L). Two peptides, ARF4L 15-24 and ARF4L 69-77, possessed the ability to induce HLA-A2-restricted and tumor-reactive CTLs from peripheral blood mononuclear cells of patients with brain tumors. Although ARF4L seemed to be ubiquitously expressed at the mRNA level, ARF4L-reactive CTLs failed to exhibit cytotoxicity against normal lymphoid blasts. These results indicate that these two ARF4L peptides could be targets for immunotherapy of HLA-A2+ patients with brain tumors.
Nonaka
Y
Y
Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan.
Tsuda
N
N
Shichijo
S
S
Ito
M
M
Maeda
Y
Y
Harada
M
M
Kamura
T
T
Shigemori
M
M
Itoh
K
K
D020727:ADP-Ribosylation Factors / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000939:Epitopes / Q000737:chemistry; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D020727:ADP-Ribosylation Factors; C116688:ARF4 protein, human