DEFECTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION IN A SARCOMATOID RENAL-CELL CARCINOMA CELL-LINE
DEFECTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION IN A SARCOMATOID RENAL-CELL CARCINOMA CELL-LINE
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DOI：
10.1097/00002371-199505000-00004
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发表时间：
1995-05-01
影响因子：
3.9
通讯作者：
ALEXANDER, RB
中科院分区：
文献类型：
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作者：
JAKOBSEN, MK;RESTIFO, NP;ALEXANDER, RB
我们研究了主要组织相容性复合体（MHC）的I类表达在12个肿瘤细胞培养系建立从转移性肾细胞癌（RCC）患者。在其中一个细胞培养系UOK 123中，我们通过流式细胞术发现没有β 2-微球蛋白（β 2-m）和MHC I类分子的表面表达。使用三种不同的单克隆抗体对β 2 m进行免疫荧光染色，结果显示在内质网（ER）、高尔基体、细胞质或细胞表面均未检测到β 2 m。没有证据表明折叠的I类分子在细胞内部或表面上;然而，ER对未折叠的I类分子染色强烈。用含有β 2 m基因的重组牛痘病毒感染UOK 123后，β 2 m的瞬时表达导致β 2 m和I类（HLA-A，B，C）决定簇的正常表达。用携带对照基因的重组牛痘载体未观察到I类或β（2）m的表达。I类分子不能到达细胞表面是由于I类MHC复合物的正确折叠和呈递需要β（2）m。不能在细胞表面组装和表达MHC I类复合物使得这些细胞不能向细胞毒性T细胞呈递抗原，并提供了逃避肿瘤免疫识别的机制。
We studied major histocompatibility complex (MHC) class I expression in 12 tumor cell culture lines established from patients with metastatic renal cell carcinoma (RCC). In one of these cell culture lines, UOK 123, we found no surface expression of beta(2)-microglobulin (beta(2)m) and MHC class I by now cytometry. Immunofluorescence staining using three different monoclonal antibodies to beta(2)m revealed no detectable beta(2)m in the endoplasmic reticulum (ER), Golgi apparatus, cytoplasm, or on the cell surface. There was no evidence of folded class I molecules inside or on the surface of the cells; however, the ER stained intensively for unfolded class I molecules. Transient expression of beta(2)m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for beta(2)m resulted in normal expression of both beta(2)m and class I (HLA-A, B, C) determinants assessed by now cytometry analysis. No expression of class I or beta(2)m was seen with the recombinant vaccinia vector carrying a control gene. The inability of class I molecules to reach the cell surface is due to the requirement of beta(2)m for proper folding and presentation of the class I MHC complex. The failure to assemble and express MHC class I complex on the cell surface renders these cells incapable of antigen presentation to cytotoxic T cells and provides a mechanism for escape from immune recognition by the tumor.