BETA-2-MICROGLOBULIN IS NOT REQUIRED FOR CELL-SURFACE EXPRESSION OF THE MURINE CLASS-I HISTOCOMPATIBILITY ANTIGEN H-2DB OR OF A TRUNCATED H-2DB

BETA-2-MICROGLOBULIN IS NOT REQUIRED FOR CELL-SURFACE EXPRESSION OF THE MURINE CLASS-I HISTOCOMPATIBILITY ANTIGEN H-2DB OR OF A TRUNCATED H-2DB
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DOI:
10.1073/pnas.83.19.7447
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发表时间:
1986-10-01
影响因子:
11.1
通讯作者:
FLAVELL, R
FLAVELL, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ALLEN, H;FRASER, J;FLAVELL, R

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β 2-微球蛋白(β 2m)被认为是将所有主要组织相容性复合体I类抗原转运至细胞表面所必需的。在此,我们表明,即使当细胞内不存在β 2m时,小鼠I类抗原H-2Db也在细胞表面表达。这是通过将H-2Db基因转染到缺乏β 2m的R1E细胞系中而建立的。由R1E转染子表达的Db抗原的构象与天然分子的构象非常不同。这种Db抗原不被Db同种异体特异性和Db限制性细胞毒性T淋巴细胞或大多数天然Db的单克隆抗体识别。我们进一步表明,Db基因的缺失构建体,它由外显子1连接到外显子4 - 8,表达截短的Db抗原缺乏结构域1和2 [Db-(1 + 2)]在细胞表面转染到R1E线后。以前的生物化学和晶体学数据表明结构域3与β 2m相关;出乎意料的是,当小鼠β 2mb基因转染到表达截短Db的R1E转染子中时,Db-(1 + 2)不与β 2m相关。这表明与结构域1和2的相互作用对于天然Db抗原中结构域3和β 2m的配对缔合是重要的。
.beta.2-Microglobulin (.beta.2m) has been thought essential for transport of all major histocompatibility complex class I antigens to the cell surface. Here, we show that the mouse class I antigen H-2Db is expressed at the cell surface even when there is no .BETA.2m present within the cell. This was established by transfecting the H-2Db gene into the R1E cell line, which lacks .BETA.2m. The conformation of the Db antigen expressed by the R1E transfectant is very different from that of the native molecule. This Db antigen is not recognized by Db-allospecific and Db-restricted cytotoxic T lymphocytes or by most monoclonal antibodies to the native Db. We show further that a deletion construct of the Db gene, which consists of exon 1 linked to exons 4-8, expresses a truncated Db antigen lacking domains 1 and 2 [Db-(1 + 2)] at the cell surface after transfection into the R1E line. Previous biochemical and crystallographic data have indicated that domain 3 is associated with .beta.2m; unexpectedly, Db-(1 + 2) does not associate with .beta.2m when the mouse .beta.2mb gene is transfected into the R1E transfectant expressing the truncated Db. This suggests that interactions with domains 1 and 2 are important for the paired association of domain 3 and .beta.2m in the native Db antigen.