RESTORATION OF ANTIGEN PRESENTATION TO THE MUTANT-CELL LINE RMA-S BY AN MHC-LINKED TRANSPORTER
RESTORATION OF ANTIGEN PRESENTATION TO THE MUTANT-CELL LINE RMA-S BY AN MHC-LINKED TRANSPORTER
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DOI：
10.1038/354528a0
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发表时间：
1991-12-19
期刊：
影响因子：
64.8
通讯作者：
HOWARD, JC
中科院分区：
文献类型：
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作者：
POWIS, SJ;TOWNSEND, ARM;HOWARD, JC
在哺乳动物细胞中，源自细胞内蛋白质的短肽展示在与主要组织相容性复合体 (MHC) 的 I 类分子相关的细胞膜上。 I 类肽复合物的表面呈现可能会提醒免疫系统注意细胞内病毒蛋白的合成。源自胞质溶胶的肽必须到达内质网池，在那里它们是组装稳定的 I 类分子 1-11 所必需的，并且有人提出，两个 MHC 编码的 ATP 结合盒 (ABC) 转运蛋白基因 12-15 的产物具有将肽递送穿过内质网膜的功能。这一想法得到了实验的支持，在这些实验中，用这些基因之一的互补 DNA 转染 I 类表达缺陷的人类细胞系可恢复细胞表面表达水平 16。在这里，我们表明，小鼠突变细胞系 RMA-S 的完整表型（其中缺乏稳定的 I 类分子的表面表达与无法呈递源自 Cytosol 6-10,17 的病毒肽相关）可通过其他转运蛋白基因的 cDNA 修复。这些结果与两个转运蛋白多肽形成异二聚体的可能性一致。
IN mammalian cells, short peptides derived from intracellular proteins are displayed on the cell membrane associated with class I molecules of the major histocompatibility complex (MHC). The surface presentation of class I-peptide complexes presumably alerts the immune system to intracellular viral protein synthesis. Peptides derived from the cytosol must reach the cisternae of the endoplasmic reticulum where they are required for the assembly of stable class I molecules 1-11, and it has been proposed that the Products of the two MHC-encoded ATP-binding cassette (ABC) transporter genes 12-15 function to deliver the peptides across the membrane of the endoplasmic reticulum. This idea is supported by experiments in which transfection of a human cell line defective in class I expression with a complementary DNA of one of these genes restored cell surface expression levels 16. Here we show that the complete phenotype of the mouse mutant cell line RMA-S, in which lack of surface expression of stable class I molecules correlates with an inability to present viral peptides originating in the Cytosol 6-10,17, is repaired by the cDNA of the other transporter gene. These results are consistent with the possibility that the two transporter polypeptides form a heterodimer.