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一种被肺癌中HLA - A24限制性肿瘤浸润淋巴细胞识别的新型内质网驻留蛋白的鉴定。

Identification of a new endoplasmic reticulum-resident protein recognized by HLA-A24-restricted tumor-infiltrating lymphocytes of lung cancer.

作者信息

Kawano K, Gomi S, Tanaka K, Tsuda N, Kamura T, Itoh K, Yamada A

机构信息

Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Japan.

出版信息

Cancer Res. 2000 Jul 1;60(13):3550-8.

Abstract

To help clarify the molecular basis of tumor immunology in lung cancer, we have investigated antigens recognized by HLA-A24-restricted CTLs established from T cells infiltrating into lung adenocarcinoma and report a new gene encoding tumor epitopes recognized by the CTLs. This gene was located on chromosome 4q31.22 and encoded an unreported endoplasmic reticulum-resident protein with 412 deduced amino acids. This protein had a molecular mass of 46 kDa and was expressed in the majority of malignant cells and tissues tested, with the exception of T-cell leukemia cells, but was not expressed in a panel of normal cells and tissues, except in those of the testis, placenta, and fetal liver. Two peptides at positions 13-20 and 75-84 were recognized by the CTLs and had an ability to induce HLA-A24-restricted and tumor-specific CTLs in peripheral blood mononuclear cells of lung cancer patients. Thus, these peptides might be appropriate molecules for use in the specific immunotherapy of HLA-A24+ patients with lung and other cancers.

摘要

为了阐明肺癌肿瘤免疫学的分子基础,我们研究了从浸润肺腺癌的T细胞建立的HLA - A24限制性细胞毒性T淋巴细胞(CTL)所识别的抗原,并报告了一个编码该CTL所识别的肿瘤表位的新基因。该基因位于4号染色体q31.22上,编码一种未报道的内质网驻留蛋白,推导的氨基酸序列有412个。该蛋白分子量为46 kDa,在大多数测试的恶性细胞和组织中表达,但T细胞白血病细胞除外,在一组正常细胞和组织中未表达,睾丸、胎盘和胎儿肝脏组织除外。CTL识别位于13 - 20位和75 - 84位的两个肽段,它们能够在肺癌患者外周血单个核细胞中诱导HLA - A24限制性和肿瘤特异性CTL。因此,这些肽段可能是用于HLA - A24 +肺癌及其他癌症患者特异性免疫治疗的合适分子。

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