Brodin Petter, Lakshmikanth Tadepally, Johansson Sofia, Kärre Klas, Höglund Petter
Department of Microbiology, Tumor and Cell Biology, Strategic Research Center for Studies of Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, [corrected] Stockholm, Sweden.
Blood. 2009 Mar 12;113(11):2434-41. doi: 10.1182/blood-2008-05-156836. Epub 2008 Oct 30.
Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I. If self-MHC is down-regulated or absent, lack of inhibition triggers "missing self" killing. NK cells developing in the absence of MHC class I are hypo-responsive, demonstrating that MHC class I molecules are required for NK-cell education. Here, we show that the number and the type of MHC class I alleles that are present during NK-cell education quantitatively determine the frequency of responding NK cells, the number of effector functions in individual NK cells, and the amount of interferon-gamma production in NK cells of specific Ly49 subsets. A relationship between the extent of inhibitory signals during education and functional responsiveness was corroborated by an enhanced probability of NK cells expressing more than one inhibitory receptor for a single host self-MHC class I allele to degranulate after activation. Our data suggest that the capacity of an individual NK cell to respond to stimulation is quantitatively controlled by the extent of inhibitory signals that are received from MHC class I molecules during NK-cell education.
自然杀伤（NK）细胞表达针对主要组织相容性复合体（MHC）I类分子的抑制性受体。如果自身MHC下调或缺失，抑制作用的缺乏会触发“自我缺失”杀伤。在缺乏MHC I类分子的情况下发育的NK细胞反应性低下，这表明MHC I类分子是NK细胞发育成熟所必需的。在此，我们表明，NK细胞发育成熟过程中存在的MHC I类等位基因的数量和类型，定量地决定了反应性NK细胞的频率、单个NK细胞中效应功能的数量，以及特定Ly49亚群的NK细胞中γ干扰素的产生量。NK细胞发育成熟过程中抑制性信号的程度与功能反应性之间的关系，通过表达针对单个宿主自身MHC I类等位基因的一种以上抑制性受体的NK细胞在激活后脱颗粒的概率增加得到了证实。我们的数据表明，单个NK细胞对刺激作出反应的能力，是由NK细胞发育成熟过程中从MHC I类分子接收的抑制性信号的程度定量控制的。
