The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product
The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product
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DOI：
10.1073/pnas.93.18.9730
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Jaffee, EM
中科院分区：
文献类型：
--
作者：
Huang, AYC;Gulden, PH;Jaffee, EM
肿瘤表达能够被肿瘤特异性细胞毒性T淋巴细胞（CTL）识别的肽抗原。用致癌物诱导的结肠直肠肿瘤CT 26（经工程改造以分泌粒细胞/巨噬细胞集落刺激因子）免疫小鼠，常规地产生短期和长期CTL系，其不仅在体外裂解亲本肿瘤，而且在体内过继转移后治愈已建立肿瘤的小鼠。当使用短期或长期CTL细粉筛选从CT 26分离的肽时，一种反相高效液相色谱肽级分始终致敏用于特异性裂解的替代靶标。在多次纯化程序后，生物活性仍然定位在一个级分内，表明实际上所有的CT 26特异性CTL识别单个肽。这一结果与其他肿瘤系统形成对比，其中已经检测到多种生物活性肽级分。该生物活性肽被鉴定为来自内源性亲嗜性小鼠白血病前病毒的包膜蛋白（gp 70）的非突变九聚体。该抗原在多种非病毒诱导的肿瘤中的选择性表达为一类独特的共享免疫显性肿瘤相关抗原作为抗肿瘤免疫的靶点提供了证据。
Tumors express peptide antigens capable of being recognized by tumor-specific cytotoxic T lymphocytes (CTL). Immunization of mice with a carcinogen-induced colorectal tumor, CT26, engineered to secrete granulocyte/macrophage colony-stimulating factor, routinely generated both short-term and long-term CTL lines that not only lysed the parental tumor in vitro, but also cured mice of established tumor following adoptive transfer in vivo. When either shortterm or long-term CTL fines were used to screen peptides isolated from CT26, one reverse-phase high performance liquid chromatography peptide fraction consistently sensitized a surrogate target for specific lysis. The bioactivity remained localized within one fraction following multiple purification procedures, indicating that virtually all of the CT26-specific CTL recognized a single peptide. This result contrasts with other tumor systems, where multiple bioactive peptide fractions have been detected. The bioactive peptide was identified as a nonmutated nonamer derived from the envelope protein (gp70) of an endogenous ecotropic murine leukemia provirus. Adoptive transfer with CTL lines specific for this antigen demonstrated that this epitope represents a potent tumor rejection antigen, The selective expression of this antigen in multiple non-viral-induced tumors provides evidence for a unique class of shared immunodominant tumor associated antigens as targets for antitumor immunity.