KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression
KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression
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DOI：
10.1182/blood-2008-10-184549
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发表时间：
2009-07-02
期刊：
影响因子：
20.3
通讯作者：
Malmberg, Karl-Johan
中科院分区：
文献类型：
--
作者：
Andersson, Sandra;Fauriat, Cyril;Malmberg, Karl-Johan
抑制性杀伤细胞免疫球蛋白样受体（KIR）保持对自身的耐受性，并塑造人类自然杀伤（NK）细胞的功能反应。在这里，我们评估了选择过程的影响，在形成抑制性KIR库的44个捐助者纯合子的A组KIR单倍型的队列。多个KIR的共表达比描述独立事件随机关联的乘积规则预期的更频繁。与该观察结果一致，KIR获得的概率随着KIR的细胞表达而增加。三种类型的KIR剧目进行了区分，不同的频率KIR和NKG 2A阳性细胞，但没有表现出依赖于自身HLA I类配体的数量。此外，自体和非自体KIR在细胞表面的分布反映了受体的随机组合，而不是同源HLA I类分子赋予的选择过程。最后，发现NKG 2A缓冲以低KIR表达频率为特征的KIR库中的整体功能反应。结果提供了新的见解抑制KIR库对人类NK细胞的形成，并支持一种模型，其中杂色KIR库产生通过顺序和随机收购的KIR在没有选择。（血。2009; 114：95-104）
Inhibitory killer cell immunoglobulin-like receptors (KIRs) preserve tolerance to self and shape the functional response of human natural killer (NK) cells. Here, we have evaluated the influence of selection processes in the formation of inhibitory KIR repertoires in a cohort of 44 donors homozygous for the group A KIR haplotype. Coexpression of multiple KIRs was more frequent than expected by the product rule that describes random association of independent events. In line with this observation, the probability of KIR acquisition increased with the cellular expression of KIRs. Three types of KIR repertoires were distinguished that differed in frequencies of KIR- and NKG2A-positive cells but showed no dependency on the number of self-HLA class I ligands. Furthermore, the distribution of self- and nonself-KIRs at the cell surface reflected a random combination of receptors rather than a selection process conferred by cognate HLA class I molecules. Finally, NKG2A was found to buffer overall functional responses in KIR repertoires characterized by low-KIR expression frequencies. The results provide new insights into the formation of inhibitory KIR repertoires on human NK cells and support a model in which variegated KIR repertoires are generated through sequential and random acquisition of KIRs in the absence of selection. (Blood. 2009; 114:95-104)