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.
http://linkedlifedata.com/resource/pubmed/chemical/ADP-Ribosylation Factors, http://linkedlifedata.com/resource/pubmed/chemical/ARF4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma
pubmed-meshheading:12472661-ADP-Ribosylation Factors, pubmed-meshheading:12472661-Antigens, Neoplasm, pubmed-meshheading:12472661-Brain Neoplasms, pubmed-meshheading:12472661-Cell Line, pubmed-meshheading:12472661-Cells, Cultured, pubmed-meshheading:12472661-Cloning, Molecular, pubmed-meshheading:12472661-Epitopes, pubmed-meshheading:12472661-HLA-A2 Antigen, pubmed-meshheading:12472661-Humans, pubmed-meshheading:12472661-Interferon-gamma, pubmed-meshheading:12472661-T-Lymphocytes, Cytotoxic
Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors.
Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan.
Journal Article, Research Support, Non-U.S. Gov't