Ly49A transgenic mice provide evidence for a major histocompatibility complex-dependent education process in natural killer cell development
Ly49A transgenic mice provide evidence for a major histocompatibility complex-dependent education process in natural killer cell development
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DOI：
10.1084/jem.185.12.2079
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发表时间：
1997-06-16
影响因子：
15.3
通讯作者：
Raulet, DH
中科院分区：
文献类型：
--
作者：
Held, W;Raulet, DH
Ly 49自然杀伤（NK）细胞受体是I类MHC特异性抑制性受体，其分布于重叠的NK细胞亚群。用在所有NK细胞中表达Ly 49 A的转基因小鼠检查Ly 49受体库的形成。在MHC I类缺陷小鼠中，Ly 49 A转基因并不能阻止内源性Ly 49基因的表达。然而，在表达Ly 49 A配体的H-2（d）小鼠中，转基因引起内源Ly 49库的明显改变。NK细胞表达另一种H-2（d）特异性受体Ly 49 G2（+）的频率大幅降低。内源性Ly 49 A mRNA水平降低表明表达内源性Ly 49 A的细胞数量减少。这些结果支持存在MHC依赖的教育过程，该过程限制了共表达多种自身特异性Ly 49受体的NK细胞的数量。还检查了Ly 49细胞表面水平的配体依赖性下调。即使转基因在低水平表达时，细胞表面也发生下调。结果表明，下调Ly 49 A细胞表面水平是一个转录后事件，并反对Ly 49受体校准到特定的细胞表面水平取决于可用的I类配体的模型。
The Ly49 natural killer (NK) cell receptors are class I MHC-specific inhibitory receptors that are distributed to overlapping NK cell subsets. The formation of the Ly49 receptor repertoire was examined with transgenic mice that express Ly49A in all NK cells. In MHC class I-deficient mice, the Ly49A transgene did not prevent expression of endogenous Ly49 genes. However, in H-2(d) mice that express a Ly49A ligand, the transgene caused clear alterations in the endogenous Ly49 repertoire. The frequency of NK cells expressing another H-2(d)-specific receptor, Ly49G2(+), was substantially reduced. Reduced numbers of cells expressing endogenous Ly49A was suggested by reduced endogenous Ly49A mRNA levels. These results support the existence of an MHC-dependent education process that limits the number of NK cells that coexpress multiple self-specific Ly49 receptors. Ligand-dependent downregulation of Ly49 cell surface levels was also examined. Cell-surface downregulation occurred even when the transgene was ex-pressed at low levels. The results demonstrate that downregulation of Ly49A cell surface levels is a posttranscriptional event, and argue against a model in which Ly49 receptors are calibrated to specific cell surface levels depending on the available class I ligands.