The impact of variation at the KIR gene cluster on human disease.
The impact of variation at the KIR gene cluster on human disease.
复制标题
KIR 基因簇变异对人类疾病的影响。
DOI：
10.1007/3-540-27743-9_12
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发表时间：
2006
影响因子：
--
通讯作者：
Martin,MP
中科院分区：
文献类型：
--
作者：
Carrington,M;Martin,MP
白细胞的行为是由配体与位于细胞表面的一组复杂的受体结合产生的抑制和刺激信号的平衡控制的。杀伤细胞免疫球蛋白样受体(KIR)基因编码自然杀伤细胞(NK)表达的受体家族之一，NK细胞是天然免疫系统的关键组成部分，通过产生细胞因子和直接细胞毒作用参与对感染或转化细胞的早期反应。KIR也表达在T细胞的一个亚群上，在那里它们有助于增强获得性免疫反应。抑制性KIR对自身HLAI类配体的识别使NK细胞能够识别正常细胞，防止NK细胞介导的针对健康自体细胞的反应。通过刺激性受体激活的NK细胞被导向I类基因表达改变的细胞，这种情况是一些病毒感染细胞和肿瘤细胞的特征。NK细胞激活的“自我缺失”模型被提出来解释对表达很少或不表达I类的细胞的杀伤，而表达正常I类的细胞则幸免于此。过去几年进行的研究表明，KIR基因座位存在广泛的多样性，这源于其多基因(基因数量取决于KIR单倍型)和多等位基因多态。鉴于KIR在免疫应答的两个方面的作用，它们对人类白细胞抗原I类异型的特异性，以及它们广泛的基因组多样性，我们有理由认为KIR基因的变异会影响对多种疾病的抵抗力和易感性。因此，KIRlocus多样性在种群内和种群间的演变可能是疾病发病率和死亡率的函数。在这里，我们回顾了越来越多的证据，声称KIR基因多态在人类疾病中的影响。
Leukocyte behavior is controlled by a balance of inhibitory and stimulatory signals generated on ligand binding to a complex set of receptors located on the cell surface. Thekiller cell immunoglobulin-like receptor (KIR)genes encode one such family of receptors expressed by natural killer (NK) cells, key components of the innate immune system that participate in early responses against infected or transformed cells through production of cytokines and direct cytotoxicity. KIRs are also expressed on a subset of T cells, where they contribute to the intensity of acquired immune responses. Recognition of self HLA class I ligands by inhibitory KIR allows NK cells to identify normal cells, preventing an NK cell-mediated response against healthy autologous cells. Activation of NK cells through stimulatory receptors is directed toward cells with altered expression of class I, a situation characteristic of some virally infected cells and tumor cells. The “missing self” model for NK cell activation was proposed to explain killing of cells that express little or no class I, while cells expressing normal levels of class I are spared. Studies performed over the last several years have revealed extensive diversity at theKIRgene locus,which stems from both its polygenic (variable numbers of genes depending onKIRhaplotype) and multiallelic polymorphism. Given the role of KIR in both arms of the immune response, their specificity for HLA class I allotypes, and their extensive genomic diversity, it is reasonable to imagine thatKIRgene variation affects resistance and susceptibility to the pathogenesis of numerous diseases. Consequently, the evolution ofKIRlocus diversity within and across populations may be a function of disease morbidity and mortality. Here we review a growing body of evidence purporting the influence ofKIRpolymorphism in human disease.