Natural killer cell acceptance of H-2 mismatch bone marrow grafts in transgenic mice expressing HLA-Cw3 specific killer cell inhibitory receptor (CD158b)
Natural killer cell acceptance of H-2 mismatch bone marrow grafts in transgenic mice expressing HLA-Cw3 specific killer cell inhibitory receptor (CD158b)
复制标题
自然杀伤细胞在表达 HLA-Cw3 特异性杀伤细胞抑制受体 (CD158b) 的转基因小鼠中接受 H-2 错配骨髓移植物
DOI：
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
É. Vivier
中科院分区：
文献类型：
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作者：
A. Cambiaggi;C. Verthuy;P. Naquet;F. Romagné;P. Ferrier;R. Biassoni;A. Moretta;L. Moretta;É. Vivier
自然杀伤（NK）细胞表达主要组织相容性复合物I类分子的杀伤细胞抑制受体（KIR）。这些表面受体的参与抑制NK细胞的细胞毒性程序。KIR也可以在T细胞亚群上表达，它们的结合类似地导致CD 3/T细胞受体复合物启动的效应器功能的抑制。KIR基因属于两个不同的家族：免疫球蛋白超家族（IgSF KIR）和二聚体C2凝集素（凝集素样KIR）。尽管在人类中发现了IgSF（p58：CD 158、p70和p140）和凝集素样KIR（CD 94/NKG 2A异源二聚体），但在小鼠中仅描述了凝集素样KIR（Ly-49家族的所有成员）。我们已经产生了表达IgSF KIR，CD 158 b（p58.2）的转基因小鼠，其识别HLA-Cw 3。我们的数据表明，CD 158 b是必要的，足以赋予NK细胞的特异性，以及在体外调节T细胞活化程序。此外，我们在CD 158 b × HLA-Cw 3双转基因小鼠中未检测到任何CD 158 b细胞表面表达对HLA I类配体表达的适应，这与小鼠中Ly-49的观察结果相反。因此，IgSF和凝集素样KIR似乎使用不同的选择/校准策略。最后，CD 158 b KIR的转基因表达防止了表达同源主要组织相容性I类HLA-Cw 3等位基因的H-2错配骨髓移植物的体内排斥，首次证明了人IgSF KIR在NK细胞功能负调节中的体内含义。
Natural killer (NK) cells express killer cell inhibitory receptors (KIRs) for major histocompatibility complex class I molecules. Engagement of these surface receptors inhibits NK cell cytotoxic programs. KIR can also be expressed on T cell subsets, and their engagement similarly results in inhibition of effector functions initiated by the CD3/T cell receptor complex. KIR genes belong to two distinct families: the immunoglobulin superfamily (IgSF KIRs) and dimeric C2 lectins (lectin-like KIRs). Whereas both IgSF (p58: CD158, p70, and p140) and lectin-like KIRs (CD94/NKG2A heterodimers) have been found in human, only lectin-like KIRs (all members of the Ly-49 family) have been described in the mouse. We have generated transgenic mice expressing an IgSF KIR, CD158b (p58.2), which recognizes HLA-Cw3. Our data show that CD158b is necessary and sufficient to confer specificity to NK cells, as well as to modulate T cell activation programs in vitro. In addition, we did not detect any adaptation of CD158b cell surface expression to that of HLA class I ligands in the CD158b × HLA-Cw3 double transgenic mice, in contrast to observations with Ly-49 in the mouse. Therefore, distinct strategies of selection/calibration appear to be used by IgSF and lectin-like KIRs. Finally, the transgenic expression of CD158b KIR prevents the in vivo rejection of H-2 mismatch bone marrow grafts, which express the cognate major histocompatibility class I HLA-Cw3 allele, demonstrating for the first time the in vivo implication of human IgSF KIRs in the negative regulation of NK cell function.
影响因子：
56.9
作者：
PHILLIPS, JH;GUMPERZ, JE;LANIER, LL
通讯作者：
LANIER, LL