Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules.
Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules.
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具有单个或多个主要组织相容性复合物I类分子的小鼠的天然杀手细胞教育。
DOI：
10.1084/jem.20050167
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发表时间：
2005-04-04
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鼠NK细胞排斥缺乏自身MHC I类表达的细胞的能力来自体内教育过程。为了研究单个MHC I类等位基因对这一过程的影响，我们产生了表达单个MHC I类等位基因（Kb、Db、Dd或Ld）或两个或更多个等位基因的组合的小鼠。所有单一MHC I类小鼠以NK细胞依赖性方式排斥MHC I类缺陷细胞。Kb或Dd的表达传达了对MHC I类缺陷细胞的强烈排斥，而Db或Ld的表达导致较弱的反应。弱配体（Db和Ld）的教育影响通过引入额外的MHC I类等位基因而进一步减弱，而强配体（Kb和Dd）在这种条件下保持其教育影响。在单一的MHC I类小鼠的激活和抑制受体的分析表明，一个给定的MHC I类分子的教育的影响是由受影响的NK细胞的数量和每个MHC I-Ly49受体相互作用的强度控制，表明NK细胞教育可能是由定性和定量事件的组合调节。
The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (Kb, Db, Dd, or Ld) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I–deficient cells in an NK cell–dependent way. Expression of Kb or Dd conveyed strong rejection of MHC class I–deficient cells, whereas the expression of Db or Ld resulted in weaker responses. The educating impact of weak ligands (Db and Ld) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (Kb and Dd) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I–Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.