Shichijo S, Nakao M, Imai Y, Takasu H, Kawamoto M, Niiya F, Yang D, Toh Y, Yamana H, Itoh K
Department of Immunology, Kurume University School of Medicine, Kurume, Japan.
J Exp Med. 1998 Feb 2;187(3):277-88. doi: 10.1084/jem.187.3.277.
Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601-restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601(+) epithelial cancer patients.
除黑色素瘤外，细胞毒性T淋巴细胞（CTL）识别的肿瘤抗原尚未明确。我们已经鉴定出一个基因，该基因编码人组织相容性白细胞抗原（HLA）-A2601限制性CTL识别的人鳞状细胞癌（SCC）的抗原肽。该基因与已知序列无相似性，编码两种（125千道尔顿和43千道尔顿）蛋白质。具有亮氨酸拉链基序的125-kD蛋白在大多数测试的增殖细胞（包括正常细胞和恶性细胞）的细胞核中表达。43-kD蛋白在来自各种器官的大多数SCC和一半的肺腺癌的细胞质中表达，但在其他癌症和一组正常组织中不表达。两种蛋白质共有的三种九肽被KE4 CTL识别，其中一种肽体外诱导外周血单核细胞（PBMC）产生针对自体肿瘤细胞的CTL。43-kD蛋白和这种九肽（KGSGKMKTE）可能对HLA-A2601（+）上皮癌患者的特异性免疫治疗有用。
