Gardiner C M, Guethlein L A, Shilling H G, Pando M, Carr W H, Rajalingam R, Vilches C, Parham P
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Immunol. 2001 Mar 1;166(5):2992-3001. doi: 10.4049/jimmunol.166.5.2992.
KIR3DL1 and KIR3DL2 are NK cell receptors for polymorphic HLA-B and -A determinants. The proportion of NK cells that bind anti-KIR3DL1-specific Ab DX9 and their level of binding vary between individuals. To determine whether these differences are due to KIR polymorphism, we assessed KIR3D gene diversity in unrelated individuals and families. Both KIR3DL1 and KIR3DL2 are highly polymorphic genes, with KIR3DS1 segregating like an allele of KIR3DL1. A KIR haplotype lacking KIR3DL1 and KIR3DS1 was defined. The two KIR3DL1 alleles of a heterozygous donor were expressed by different, but overlapping, subsets of NK cell clones. Sequence variation in KIR3DL1 and KIR3DL2 appear distinct; recombination is more evident in KIR3DL1, and point mutation is more evident in KIR3DL2. The KIR3DL1 genotype correlates well with levels of DX9 binding by NK cells, but not with the frequency of DX9-binding cells. Different KIR3DL1 alleles determine high, low, and no binding of DX9 Ab. Consequently, heterozygotes for high and low binding KIR3DL1 alleles have distinct subpopulations of NK cells that bind DX9 at high and low levels, giving characteristic bimodal distributions in flow cytometry. The Z27 Ab gave binding patterns similar to those of DX9. Four KIR3DL1 alleles producing high DX9 binding phenotypes were distinguished from four alleles producing low or no binding phenotypes by substitution at one or more of four positions in the encoded protein: 182 and 283 in the extracellular Ig-like domains, 320 in the transmembrane region, and 373 in the cytoplasmic tail.
KIR3DL1和KIR3DL2是针对多态性HLA - B和 - A决定簇的自然杀伤（NK）细胞受体。结合抗KIR3DL1特异性抗体DX9的NK细胞比例及其结合水平在个体间存在差异。为了确定这些差异是否归因于KIR多态性，我们评估了无关个体和家族中的KIR3D基因多样性。KIR3DL1和KIR3DL2都是高度多态的基因，KIR3DS1像KIR3DL1的一个等位基因那样分离。定义了一种缺乏KIR3DL1和KIR3DS1的KIR单倍型。杂合供体的两个KIR3DL1等位基因由不同但重叠的NK细胞克隆亚群表达。KIR3DL1和KIR3DL2中的序列变异似乎不同；重组在KIR3DL1中更明显，而点突变在KIR3DL2中更明显。KIR3DL1基因型与NK细胞对DX9的结合水平密切相关，但与DX9结合细胞的频率无关。不同的KIR3DL1等位基因决定了DX9抗体的高、低结合以及无结合情况。因此，高结合和低结合KIR3DL1等位基因的杂合子具有以高、低水平结合DX9的不同NK细胞亚群，在流式细胞术中呈现出特征性的双峰分布。Z27抗体产生的结合模式与DX9相似。通过编码蛋白中四个位置（细胞外免疫球蛋白样结构域中的182和283、跨膜区域中的320以及胞质尾中的373）中一个或多个位置的替换，区分出了产生高DX9结合表型的四个KIR3DL1等位基因与产生低结合或无结合表型的四个等位基因。
