TISSUE-SPECIFIC AND CELL-SURFACE EXPRESSION OF HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HEAVY (HLA-B7) AND LIGHT (BETA-2-MICROGLOBULIN) CHAIN GENES IN TRANSGENIC MICE
TISSUE-SPECIFIC AND CELL-SURFACE EXPRESSION OF HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HEAVY (HLA-B7) AND LIGHT (BETA-2-MICROGLOBULIN) CHAIN GENES IN TRANSGENIC MICE
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DOI：
10.1073/pnas.85.20.7690
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发表时间：
1988-10-01
影响因子：
11.1
通讯作者：
WEISSMAN, SM
中科院分区：
文献类型：
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作者：
CHAMBERLAIN, JW;NOLAN, JA;WEISSMAN, SM
我们将编码人主要组织相容性复合体I类抗原的重链（HLA-B7）和轻链[β 2-微球蛋白（β 2 m）]的人基因HLA-B7和B2 M导入不同系的转基因小鼠中。HLA-B7 RNA表达的组织特异性模式与内源性I类H-2基因相似，尽管HLA-B7基因在肝脏中表达不足约10倍。无论HLA-B7基因含有12或0.66 kb的5“侧翼序列，都检测到相同的RNA表达模式。表达水平是拷贝数依赖性的，并且与H-2基因的表达水平一样有效;干扰素增强HLA-B7 RNA的表达平行于H-2。除了负责γ的机制之外，干扰素增强的表达，必须有至少一个其他组织特异性机制控制I类RNA的组成水平。组织特异性人β 2 m RNA表达与小鼠β 2 m相似，包括在肝脏中的高水平表达。与HLA-B7单转基因小鼠相比，HLA-B7/B2 M双转基因小鼠的T细胞和胸腺细胞亚群上的细胞表面HLA-B7增加了10至17倍。HLA-B7在胸腺细胞上的表达模式类似于H-2K，而不是H-2D。这些结果证实了两条人链的共表达是有效的表面表达所必需的，并且HLA-B7可能与H-2K共享调节机制，这使其与H-2D区分开来。
We introduced the human genes HLA-B7 and B2M encoding the heavy (HLA-B7) and light [.beta.2-microglobulin (.beta.2m)] chains of a human major histocompatibility complex class I antigen into separate lines of transgenic mice. The tissue-specific pattern of HLA-B7 RNA expression was similar to that of endogenous class I H-2 genes, although the HLA-B7 gene was about 10-fold underexpressed in liver. Identical patterns of RNA expression were detected whether the HLA-B7 gene contained 12 or 0.66 kilobase(s) (kb) of 5'' flanking sequence. The level of expression was copy number dependent and as efficient as that of H-2 genes; .gamma. interferon enhanced HLA-B7 RNA expression in parallel to that of H-2. In addition to the mechanism(s) responsible for .gamma. interferon-enhanced expression, there must be at least one other tissue-specific mechanism controlling the constitutive levels of class I RNA. Tissue-specific human .beta.2 m RNA expression was similar to that of mouse .beta.2 m, including high-level expression in liver. Cell surface HLA-B7 increased 10- to 17-fold on T cells and on a subset of thymocytes from HLA-B7/B2M doubly transgenic mice compared to HLA-B7 singly transgenic mice. The pattern of expression of HLA-B7 on thymocytes resembled that of H-2K as opposed to H-2D. These results confirm that coexpression of both human chains is required for efficient surface expression and that HLA-B7 may share a regulatory mechanism with H-2K, which distinguishes it H-2D.