Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer.
Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer.
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DOI：
10.1084/jem.164.5.1516
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发表时间：
1986-11-01
期刊：
影响因子：
--
通讯作者：
Schreiber H
中科院分区：
文献类型：
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作者：
Stauss HJ;Van Waes C;Fink MA;Starr B;Schreiber H
肿瘤特异性移植抗原是可以导致同基因宿主对移植癌症进行完全免疫破坏的抗原。当此类抗原在由化学或物理致癌剂诱导的癌症上表达时，它们通常是独特的，即对于每个独立诱导的肿瘤具有不同的抗原性。在这项研究中，我们表明，从小鼠紫外线诱导的回归肿瘤 1591 中分离出编码新型 MHC I 类分子的基因产物，代表了一种导致肿瘤排斥的独特肿瘤特异性移植抗原。主要证据来自我们的发现，即 1591 个进展变体经常丢失编码这种抗原的基因，该基因在亲本肿瘤中表达，但在正常小鼠中会消退；此外，通过DNA转染将该基因重新引入1591进展变体中，导致进展变体在正常免疫活性小鼠中消退。因此，转染后进展肿瘤恢复到亲本回归表型。与转染后新型 MHC I 类基因的表达导致回归表型的结论一致，我们还发现，失去转染基因表达的转染肿瘤变体恢复了其进行性生长行为。最后，我们表明，由新型 I 类基因编码的分子可以被同源肿瘤特异性溶细胞 T 细胞克隆特异性识别，我们之前已经证明该克隆可以在体外从亲本回归肿瘤细胞系中选择进展变体。其他高免疫原性回归肿瘤的独特肿瘤特异性排斥抗原在多大程度上是由新型 MHC I 类基因编码的，以及这些基因是否代表致癌剂治疗引起的种系突变或体细胞突变，仍有待确定。
Tumor-specific transplantation antigens are antigens that can lead to complete immunological destruction of a transplanted cancer by the syngeneic host. When such antigens are expressed on cancers induced by chemical or physical carcinogens, then they are usually unique, i.e., antigenically different for each independently induced tumor. In this study, we show that the product of a gene encoding a novel MHC class I molecule and isolated from the murine UV light-induced regressor tumor 1591 represents one such unique tumor-specific transplantation antigen that causes tumor rejection. The major evidence comes from our finding that 1591 progressor variants regularly lost the gene encoding this antigen that is expressed in the parental tumor that regresses in normal mice; furthermore, reintroduction of this gene into a 1591 progressor variant by DNA transfection caused the progressor variant to regress in normal immunocompetent mice. Thus, the progressor tumor reverted to the parental regressor phenotype following transfection. Consistent with the conclusion that the expression of the novel MHC class I gene following transfection was responsible for the regressor phenotype is also our finding that a variant of the transfected tumor that had lost expression of the transfected gene resumed its progressive growth behavior. Finally, we show that the molecule encoded by the novel class I gene is specifically recognized by a syngeneic tumor-specific cytolytic T cell clone that we have previously shown to select in vitro for progressor variants from the parental regressor tumor cell line. It remains to be determined to what extent unique tumor-specific rejection antigens of other highly immunogenic regressor tumors are encoded by novel MHC class I genes and whether these genes represent germline mutations or somatic mutations caused by the carcinogen treatment.