A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes.

A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes.
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DOI:
10.1084/jem.187.3.277
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发表时间:
1998-02-02
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Itoh K
Itoh K
中科院分区:
其他
文献类型:
--
作者:
Shichijo S;Nakao M;Imai Y;Takasu H;Kawamoto M;Niiya F;Yang D;Toh Y;Yamana H;Itoh K

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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确定。我们已经确定了一个基因编码的抗原肽的人鳞状细胞癌(SCC)识别的人类组织相容性白细胞抗原(HLA)-A2601限制性CTL。该基因与已知序列没有相似性,编码两种(125和43 kD)蛋白质。亮氨酸拉链基序的125-kD蛋白质在大多数增殖细胞的细胞核中表达,包括正常和恶性细胞。43-kD蛋白表达在大多数SCC的细胞质中,从各种器官和一半的肺腺癌,但不表达在其他癌症,也没有在面板的正常组织。这两种蛋白共有的三个九肽被KE4 CTL识别,并且其中一个肽在体外从外周血单个核细胞(PBMC)诱导的CTL仅限于自体肿瘤细胞。43-kD蛋白和该九肽(KGSGKMKTE)可用于HLA-A2601+上皮癌患者的特异性免疫治疗。
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.