MHC class I-specific inhibitory receptors and their ligands structure diverse human NK-cell repertoires toward a balance of missing self-response
MHC class I-specific inhibitory receptors and their ligands structure diverse human NK-cell repertoires toward a balance of missing self-response
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DOI：
10.1182/blood-2008-03-143727
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发表时间：
2008-09-15
期刊：
影响因子：
20.3
通讯作者：
Parham, Peter
中科院分区：
文献类型：
--
作者：
Yawata, Makoto;Yawata, Nobuyo;Parham, Peter
利用高维流式细胞术研究了6种抑制性HLA i类特异性受体在58人原代NK细胞上的不同表达，以了解NK细胞库的结构和功能。每个库中存在64个表达所有可能受体组合的亚群，并且受体无细胞的频率在供者中有所不同。NK亚群之间缺失自我反应的增强有很大差异，而亚群反应是由供体KIR/HLA同种异体定义的，这反映了抑制受体及其配体之间相互作用的差异。这与NKG2A的增强作用形成了对比，NKG2A的增强作用是恒定的，强度中等。我们推断出一种调节显示不同水平缺失自我反应的NK亚群频率的机制，该系统减少了显示过强或过弱反应的kir表达亚群的存在，并有效地将其替换为库中表达nkg2a的细胞。通过这种高分辨率的抑制受体表达分析，根据NKG2A(+)/NKG2A（-）细胞的含量、受体缺失细胞的频率和KIR受体共表达的程度，定义了5种nk细胞库。这些分析为如何构建个性化的人类nk细胞库提供了新的视角。
Variegated expression of 6 inhibitory HLA class I-specific receptors on primary NK cells was studied using high-dimension flow cytometry in 58 humans to understand the structure and function of NK-cell repertoires. Sixty-four subsets expressing all possible receptor combinations were present in each repertoire, and the frequency of receptor-null cells varied among the donors. Enhancement in missing-self response between NK subsets varied substantially where subset responses were defined by donor KIR/HLA allotypes, reflecting the differences in interaction between inhibitory receptors and their ligands. This contrasted to the enhancement conferred by NKG2A, which was constant and of intermediate strength. We infer a mechanism that modulates frequencies of the NK subsets displaying diverse levels of missing-self response, a system that reduces the presence of KIR-expressing subsets that display either too strong or too weak a response and effectively replaces them with NKG2A-expressing cells in the repertoire. Through this high-resolution analysis of inhibitory receptor expression, 5 types of NK-cell repertoire were defined by their content of NKG2A(+)/NKG2A(-) cells, frequency of receptor-null cells, and degree of KIR receptor coexpression. The analyses provide new perspective on how personalized human NK-cell repertoires are structured.