Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells
Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells
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DOI：
10.4049/jimmunol.176.12.7511
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Makrigiannis, Andrew P.
中科院分区：
文献类型：
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作者：
Carlyle, James R.;Mesci, Aruz;Makrigiannis, Andrew P.
NK1.1异体抗原的表达可用于确定某些小鼠品系的NK细胞，如B6 （NKR-P1C）和SJL （NKR-P1B）。然而，BALB/c NK细胞不与抗nk1.1单抗PK136发生反应。为了研究BALB/c NK细胞的NK1.1（-）表型，我们对BALB/c Nkrp1区域进行了NK1.1表位定位和基因组分析。细菌人工染色体文库分析显示，与Ly49区域不同，Nkrp1-Ocil/Clr区域在B6和BALB/c小鼠之间表现出有限的遗传差异。事实上，显著的差异仅限于Nkrp1b和Nkrp1c基因。引人注目的是，B6 Nkrp1d基因在BALB/c小鼠和其他菌株中似乎代表了Nkrp1b基因的不同等位基因。重要的是，BALB/c NK细胞表达丰富且功能性的Nkrp1转录物，并且BALB/c Nkrp1 - p1b受体可以功能性地结合Ocil/Clr-b配体。然而，BALB/c NKR-P1B/ c序列与已知的NK1.1同种抗原不同，并且表位定位表明，NKR-P1B（BALB）蛋白中单个氨基酸的定向突变赋予NK1.1反应性。因此，PK136 mAb部分识别NKR-P1B（Sw/SJL）和NKR-P1C（B6）中存在的远端c端表位，但在NKR-P1A/D/F-B6和NKR-P1B/C-BALB中不存在。Nkrp1b/c基因产物的等位基因分化和BALB/c Nkrp1-Ocil/Clr区域的有限分化解释了长期以来关于小鼠NK细胞株特异性NK1.1异体抗原反应性的困惑。
NK1.1 alloantigen expression can be used to define NK cells in certain mouse strains, such as B6 (NKR-P1C) and SJL (NKR-P1B). However, BALB/c NK cells do not react with the anti-NK1.1 mAb, PK136. To investigate the NK1.1(-) phenotype of BALB/c NK cells, we have undertaken NK1.1 epitope mapping and genomic analysis of the BALB/c Nkrp1 region. Bacterial artificial chromosome library analysis reveals that, unlike the Ly49 region, the Nkrp1-Ocil/Clr region displays limited genetic divergence between B6 and BALB/c mice. In fact, significant divergence is confined to the Nkrp1b and Nkrp1c genes. Strikingly, the B6 Nkrp1d gene appears to represent a divergent allele of the Nkrp1b gene in BALB/c mice and other strains. Importantly, BALB/c NK cells express abundant and functional Nkrp1 transcripts, and the BALB/c NKR-P1B receptor functionally binds Ocil/Clr-b ligand. However, the BALB/c NKR-P1B/C sequences differ from those of the known NK1.1 alloantigens,, and epitope mapping demonstrates that directed mutation of a single amino acid in the NKR-P1B(BALB) protein confers NK1.1 reactivity. Thus, PK136 mAb recognizes, in part, a distal C-terminal epitope present in NKR-P1B(Sw/SJL) and NKR-P1C(B6), but absent in NKR-P1A/D/F-B6 and NKR-P1B/C-BALB. Allelic divergence of the Nkrp1b/c gene products and limited divergence of the BALB/c Nkrp1-Ocil/Clr region explain a longstanding confusion regarding the strain-specific NK1.1 alloantigen reactivity of mouse NK cells.