Enhanced expression of class I major histocompatibility complex gene (Dk) products on immunogenic variants of a spontaneous murine carcinoma.
Enhanced expression of class I major histocompatibility complex gene (Dk) products on immunogenic variants of a spontaneous murine carcinoma.
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I 类主要组织相容性复合体基因 (Dk) 产物在自发性鼠癌免疫原性变体上的表达增强。
DOI：
10.1093/jnci/75.2.291
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
B. Elliott
中科院分区：
文献类型：
--
作者：
D. A. Carlow;R. Kerbel;J. T. Feltis;B. Elliott
免疫原性和非免疫原性的变异克隆是从最近获得的自发性小鼠腺癌处理后（异种化）与诱变剂甲磺酸乙酯或DNA低甲基化剂，和“基因激活剂”，5-氮杂胞苷。未处理的肿瘤群体的克隆分析证实，免疫原性变体是异种化方案的结果。在每只小鼠10（6）个细胞的剂量下，非免疫原性变体，如亲本肿瘤系，在正常的同基因受体中进行性生长。相比之下，免疫原性变体在正常同基因小鼠中被排斥，并且仅在T细胞缺陷的裸鼠中进行性生长。相应的克隆变体的血清学分析显示，免疫原性变体表达的I类H-2Dk抗原水平相对于亲本或非免疫原性细胞系显著升高（4倍至10倍）。表现出边缘免疫原性的两个变体表达高水平和低水平的主要组织相容性复合体（MHC）抗原，分别表明升高的MHC表达，虽然可能是一个促成因素，并没有占在所有情况下的免疫原性表型。最后，两种变体的免疫原性表型在培养中随时间衰减。在逆转过程中的克隆失去了其升高的Dk基因表达，并在正常的同基因小鼠中逐渐变得更具致瘤性。总之，这些数据与一个假设是一致的，即升高的MHC表达可以导致最初低MHC表达肿瘤的免疫原性表型，并且在某些临床癌症中观察到的MHC水平降低可能对肿瘤-宿主关系的免疫学方面具有重要意义。
Both immunogenic and nonimmunogenic variant clones were isolated from a recently obtained spontaneous murine adenocarcinoma after treatment (xenogenization) with either the mutagen ethyl methanesulfonate or the DNA hypomethylating agent, and "gene activator," 5-azacytidine. Clonal analysis of the untreated tumor population confirmed that immunogenic variants arose as a consequence of the xenogenization protocol. At a dose of 10(6) cells per mouse, nonimmunogenic variants, like the parental tumor line, grew progressively in normal syngeneic recipients. In contrast, immunogenic variants were rejected in normal syngeneic mice and grew progressively only in T-cell-deficient nude mice. Serologic analysis of the respective clonal variants revealed that immunogenic variants expressed substantially elevated (fourfold to tenfold) levels of class I H-2Dk antigen relative to parental or nonimmunogenic cell lines. Two variants exhibiting marginal immunogenicity expressed high and low levels of major histocompatibility complex (MHC) antigen, respectively suggesting that elevated MHC expression, although possibly a contributing factor, did not account for the immunogenic phenotype in all cases. Finally, the immunogenic phenotype of two variants decayed with time in culture. Clones in the process of reversion lost their elevated Dk gene expression and became progressively more tumorigenic in normal syngeneic mice. Together, these data are consistent with a hypothesis that elevated MHC expression can contribute to the immunogenic phenotype of originally low MHC-expressing tumors and that the reduced level of MHC observed in certain clinical cancers may have significant implications with regard to immunologic aspects of the tumor-host relationship.