Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype
Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype
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DOI：
10.4049/jimmunol.168.5.2307
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
Parham, P
中科院分区：
文献类型：
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作者：
Shilling, HG;Guethlein, LA;Parham, P
杀伤免疫球蛋白样受体（KIR）基因是人类19号染色体上的一个多基因家族。KIR基因在不同的单倍型上以各种组合出现。此外，KIR基因是多态性的。为了研究等位基因多态性如何使具有相似或相同KIR基因组合的KIR单倍型多样化，我们设计了用于区分KIR 2DL 1、-2DL3、-3DL1和-3DL2等位基因的方法。应用这些方法对来自34个家系的143个个体进行了98个独立的KIR单倍型的分析。还鉴定了三个新的3DL 2等位基因和嵌合3DL 1/3DL 2序列。在A组单倍型中，2DL 1、2DL 3、3DL 1和3DL 2等位基因的22种不同组合。在明确确定的B组单倍型中，有15种不同的单倍型，涉及9种不同的KIR基因组合。A和B单倍型在2DL 1和2DL 3等位基因之间以及3DL 1和3DL 2等位基因之间均表现出较强的连锁不平衡（LD）。相反，在限定KIR基因复合物的两半的2DL 1/2DL 3和3DL 1/3DL 2对之间几乎没有LD。等位基因多态性和可变基因含量的协同组合使KIR基因型个体化到无关个体几乎总是具有不同KIR类型的程度。这种多样性水平可能反映了病原体对人类NK细胞反应的强大压力。免疫学杂志，2002，168：2307-2315.
Killer Ig-like receptor (KIR) genes are a multigene family on human chromosome 19. KIR genes occur in various combinations on different haplotypes. Additionally, KIR genes are polymorphic. To examine how allelic polymorphism diversifies KIR haplotypes with similar or identical combinations of KIR genes, we devised methods for discriminating alleles of KIR2DL1, -2DL3, -3DL1, and -3DL2. These methods were applied to 143 individuals from 34 families to define 98 independent KIR haplotypes at the allele level. Three novel 3DL2 alleles and a chimeric 3DL1/3DL2 sequence were also identified. Among the A group haplotypes were 22 different combinations of 2DL1, 2DL3, 3DL1, and 3DL2 alleles. Among the B group haplotypes that were unambiguously determined were 15 distinct haplotypes involving 9 different combinations of KIR genes. A and B haplotypes both exhibit strong linkage disequilibrium (LD) between 2DL1 and 2DL3 alleles, and between 3DL1 and 3DL2 alleles. In contrast, there was little LD between the 2DL1/2DL3 and 3DL1/3DL2 pairs that define the two halves of the KIR gene complex. The synergistic combination of allelic polymorphism and variable gene content individualize KIR genotype to an extent where unrelated individuals almost always have different KIR types. This level of diversity likely reflects strong pressure from pathogens on the human NK cell response. The Journal of Immunology, 2002, 168: 2307-2315.