Distribution of killer cell immunoglobulin-like receptors in the Greek population

The interaction between killer cell immunoglobulin-like receptors (KIR) expressed on natural killer (NK) cells, and human leukocyt antigen (HLA) molecules expressed on target cells is known to regulate the cytolytic activity. A wide range of KIR genotypes is observed in the population, as the number of KIR loci can vary. In the present study we have determined the frequencies and combinations of 13 KIR genes and two CD94:NKG2 receptor genes and their distribution in the two haplotype groups in a panel of 233 unrelated healthy Greek Caucasians. We have typed genomic DNA for the presence of the putative KIR loci KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR3DL3, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 using modified polymerase chain reaction sequence-specific primers. The frequency of KIR loci combined with the linkage disequilibrium values suggest that the Greek population shares several general features with other Caucasoid populations studied before, but still distinguishes itself by the increased or decreased frequency of several alleles. The majority of the 45 different KIR genotypes seen in Greeks have been observed in Caucasoid populations studied before. Nevertheless, two of these genotypes, although met in other populations, have not been found in Caucasians before. One individual possesses a novel profile with no KIR inhibitory gene. The A haplotypes remain the most prevalent, with AA1 being the most common genotype, and the number of inhibitory KIRs being more variable than the number of noninhibitory KIRs in most haplotypes.     

The distribution of genetic diversity of KIR genes in the Chinese Mongolian population

Killer cell immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and as such regulate their response against infection and malignancy. KIR genes are variable in gene content and type, which results in different KIR haplotypes, and can be used to discriminate individuals and populations from different regions or ethnic groups. In the present study, we represent the first report on the KIR gene frequency and content diversities of 14 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and 2 pseudogenes (KIR3DP1 and 2DP1) in the Chinese Mongolian population. The 16 detected KIR genes were all observed. All the individuals were typed positive for the four framework genes KIR3DL3, 3DL2, 2DL4 and the pseudogene KIR3DP1, as well as for the pseudogene KIR2DP1. The observed carrier gene frequencies (OF) of the other KIR genes ranged from 16% at the KIR2DL2 locus to 93% at the KIR3DL1 locus. Over all, 48 different gene profiles were found in the study population and the most commonly observed KIR gene profile with a frequency of 14% consisted of KIR2DL4, 3DL2, 3DL3, 2DP1, 3DP1, 2DL1, 2DL3 and 3DL1 which belongs to the AA genotype. Principal component analysis (PCA) and the dendrogram illustrated the genetic distances between our study population and previously published populations from other ethnic groups or regions. The results of the present study show that the KIR gene family is highly polymorphic and can be a valuable tool for enriching the Chinese ethnical gene information resources, for anthropological studies, as well as for KIR gene related disease research.     

Distribution of KIR genes in the Iranian population

Killer-cell immunoglobulin-like receptors (KIR) are a family of inhibitory and activating receptors that are expressed mainly by natural killer cells. The KIR gene family is highly polymorphic, and its genomic diversity is achieved through differences in gene content as well as allelic polymorphism. The number of KIR loci has been reported to be various among individuals and therefore resulting in different KIR haplotypes. This study represents the first report on the distribution of 17 presently defined KIR genes and pseudogenes in the Iranian population. In our study, 200 unrelated healthy individuals were KIR typed by a novel polymerase chain reaction–sequence-specific primers genotyping assay, and Iranian KIR genes distribution was compared with other ethnic groups. Over all, twenty-six different genotype profiles were found in our population and all KIR genes were observed. The most frequent non-framework KIR genes detected in our population were KIR2DL1 (96.5%), KIR3DL1 (91.5%), KIR2DS4 (91.5%) and the pseudogene KIR2DP1 (96.5%). The most commonly observed KIR genotype in Iranian population with a frequency of 27.5% consisted of KIR2DL1 , KIR2DL3 , KIR2DL4 , KIR3DL1 , KIR3DL2 , KIR3DL3 and KIR2DS4 genes and the pseudogenes KIR2DP1 and KIR3DP1 , which was compatible with a homozygote group-A haplotype. In addition, we found a new genotype ( KIR2DL2 , KIR2DL4 , KIR2DL5 , KIR3DL2 , KIR3DL3 , KIR2DS2 , KIR2DS3 , KIR2DS5 , KIR3DS1 and KIR3DP1 ) in our samples. The results show that distribution of KIR genes in the Iranian population has common general features with the Caucasian populations studied before but still with unique, decreased or increased frequencies of several loci.     

Diversity distributions of killer cell immunoglobulin-like receptor genes and their ligands in the Chinese Shaanxi Han population

In the present study, 17 killer cell immunoglobulin-like receptors (KIR) genes and KIR ligands (human leukocyte antigen [HLA] -A and -B) were detected by using a polymerase chain reaction-sequence-specific primer (PCR-SSP) method in 104 unrelated healthy Han individuals living in Shaanxi province, China. The observed carrier frequencies of the 12 KIR genes ranged from 0.14 to 0.96. KIR2DL4, 3DL2, 3DL3, 2DP1 and 3DP1 were found to be present in every individual. A total of 51 different KIR gene profiles were identified, in which 11 gene profiles exclusively belonged to the study population. Neighbor-joining phylogenetic tree between the studing population and its neighboring ethnic groups was constructed using the observed carrier frequencies of 13 KIR loci. The phylogenetic tree shows that the Shaanxi Han population, Han populations in different regions, Yi, Japanese, and Koreans were in the same cluster. KIR/HLA relationships show that KIR3DS1(-)/3DL1(+)/Bw4(+) was the most common association in the population. In conclusion, the present study findings reveal the high polymorphism of KIRs in the Shaanxi Han population, demonstrate the KIR/HLA association in the study population, and enrich the KIR and HLA gene resources. The obtained KIR data will further the understanding of genetic relationships among populations in different geographic areas, and assist in answering questions regarding KIR/HLA relationships.     

Distribution of killer-cell immunoglobulin-like receptor (KIR) in Comoros and Southeast France

Killer-cell immunoglobulin-like receptors (KIRs) expressed by natural killer cells are cell surface molecules able to recognize groups of HLA class I alleles. The number and distribution of KIR genes vary among individuals and populations. The aim of this study is to analyse the KIR gene content in a Comorian population in order to investigate genetic relationships with other populations and to reconstruct past migration events. The Comorian population consisted of 54 unrelated immigrants living in France and a control population consisted of 38 individuals from Southeast France. We investigated the presence or absence of 15 KIR genes, two pseudogenes expressed and non-expressed forms of KIR2DL5 and the two major subtype full-length and deleted forms of KIR2DS4. All individuals were typed positive for the framework genes, i.e. KIR2DL4, KIR3DL2 and KIR3DL3, and the two pseudogenes KIR3DP1 and KIR2DP1. The frequencies of full-length KIR2DS4 (*00101/00102/002) were lower in the French population (F = 29%) than in the Comorian population (F = 72%) (P(c) < 0.05). No significant differences were found for other KIR genes. A total of 11 genotypes were identified in the Southeast French population and 22 genotypes in the Comorian population. The most common genotype (2DL1, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3 and 2DS4) accounted for 41% in the Comorian population and 34% in the Southeast French population. Principal component analysis using KIR gene data from 20 populations was performed to determine genetic differences and relations between populations. The Comorian population exhibited closest kinship with Africans and Asians. As KIR gene content is heterogeneous among ethnic groups, it can probably be used to assess the genetic relationships among populations from different geographic areas.     

Investigation of killer cell immunoglobulin-like receptor KIR2DL4 diversity by sequence-based typing in Chinese population

Human killer cell immunoglobulin-like receptors (KIRs) play an important role in controlling natural killer (NK) cell function. Here, polymerase chain reaction sequence-based typing (PCR-SBT) procedures identifying alleles of the KIR2DL4 gene have been established. The method was designed around the specific amplification of exon 3 to exon 5 and exon 7 to exon 9 of the KIR2DL4 gene and produce discrimination of KIR2DL4 alleles. Genomic DNAs from 83 healthy unrelated Chinese Han individuals were typed for KIR2DL4 alleles by this method. Each sample was assigned to the putative KIR2DL4 allele combination according to the nucleotide polymorphism profiles of all KIR2DL4 alleles. Twenty-one different genotypes and seven KIR2DL4 alleles were observed in the population, with KIR2DL4*00102 having the highest frequency, 0.5. Five individuals bear a recombinant allele KIR3DP*004 that associated with three putative KIR2DL4 alleles. Our data demonstrated that the established PCR-SBT method for KIR2DL4 allele typing was reliable, and Chinese Han population is distinct in KIR2DL4 allele frequencies in comparison to some other populations.     

Genomic diversity of natural killer cell receptor genes in three populations

We report the distribution of genes encoding 11 killer cell immunoglobulin-like receptors (KIR) and 2 CD94:NKG2 receptors, in 32 Caucasians, 67 Australian Aborigines and 59 Vietnamese. The inhibitory and the activating KIR genes were found at different frequency in the three populations. No correlation was found between the polymorphism of the KIR genes and the HLA specificities of the tested samples. The most significant KIR associations were 2DL2 with 2DS2; 2DL2 with 2DS3 and 3DL1 with 2DS4 in all three study groups. In Caucasians and Vietnamese 2DS2 was associated with 2DS3 and 2DS1with 3DS1. KIR 2DL1 was strongly associated with three other KIRs: 2DL3, 3DL1 and 2DS4 in Aborigines. The distribution of the KIR phenotypes was different in the three populations. The AA1 phenotype was frequent in Vietnamese (42.4%) and Caucasians (31.2%), but very rare in Aborigines (1.5%). In contrast, the BB7 phenotype was very common for Aborigines (22.4%) and was absent in the two other groups. Our data demonstrate that different associations and putative KIR haplotypes could be distinguished in different populations.     

Diversity of killer cell immunoglobulin-like receptor genes in the Bai ethnic minority of Yunnan, China

Killer cell immunoglobulin-like receptors (KIRs), expressed in both natural killer (NK) cells and a subset of T cells, represent a family of both inhibitory and activating receptors that can regulate NK and T cells upon interacting with human leucocyte antigen (HLA) class I molecules on target cells. The number and distribution of KIR genes vary between individuals and populations from different geographical regions and ethnic origins. In this study, we investigated KIR gene frequencies and genotype diversities of 13 KIR genes, 2 pseudogenes, expressed and non-expressed forms of KIR2DL5 and the two subtypes, full-length and deleted forms, of KIR2DS4 in 100 unrelated healthy individuals of the Bai population, living in the Dali Bai autonomous prefecture in the Yunnan province. All individuals were typed positive for the three framework loci KIR3DL3, 2DL4 and 3DL2, as well as for three non-framework genes KIR2DL1, 2DL3 and the pseudogene KIR2DP1. The gene frequencies of the other KIR genes ranged from 7%-95%. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that they display a wide range of LD. χ2 analysis among non-ubiquitous genes, using the KIR gene frequency data from our study population, as well as from previously published population data, was conducted and revealed significant differences in the KIR2DL1, 2DL2, 3DL1 and KIR2DS1 genes. The results of the present study can be valuable for enriching the Chinese ethnic gene information resources of the KIR gene pool, for anthropological studies, as well as for KIR-related disease research.     

Distribution of killer cell immunoglobulin-like receptor genes in the Chinese Han population

Killer cell immunoglobulin-like receptors (KIRs) on natural killer cells recognize groups of HLA class I alleles. Seventeen KIR genes have been identified at present, and two kinds of KIR haplotypes (group A and B) have been described based on their gene contents. Immunogenetic analysis of different ethnic populations shows significant differences in terms of the distribution of group A and B haplotypes. Here, genomic DNA from 104 healthy unrelated Chinese Han individuals was typed for the presence or absence of KIR genes. All 17 KIR genes were observed in the population, and framework genes 3DL3, 3DP1, 2DL4, and 3DL2 were present in all individuals. Twenty-six different genotypes were found, four of which could not be assigned to haplotypes according to the model of Hsu et al. (J Immunol 2002: 169: 5118). Group A haplotypes outnumbered group B haplotypes in frequency by approximately 3:1, with individuals having two group A haplotypes accounting for 58.7%. Analysis indicated that some pairs of KIR genes showed remarkable linkage disequilibrium. Our data demonstrated that the Chinese Han population is distinct in KIR gene frequencies and putative KIR haplotypes in comparison to some other populations.     

Characterization of human killer immunoglobulin-like receptors (KIRs) among healthy Saudis

Genes encoding KIRs vary in frequency among different populations and ethnic groups. This study investigated the KIR gene frequency distribution in 148 healthy unrelated Saudi subjects and compared the results with other published findings. All inhibitory and activating KIR genes were present at variable frequencies, with A haplotype-associated genes (KIR2DL1, -2DL3, -3DL1, and KIR2DS4) being observed at higher frequencies (88.9–99.5%) than B haplotype-associated genes (KIR2DS1, -2DS2, -2DS3, -2DS5, -2DL5 and -2DL2) (31.1–70.1%). Thirty-one different KIR genotypes were observed, and AA genotypes displayed the highest frequency (18.2%). This Saudi population possesses similar KIR gene distributional characteristics to those reported in other neighboring populations (e.g., Lebanese) and shows disparities in certain genes and gene contents from other populations (e.g., Australian Aborigines). These findings can be used as a reference control in future studies evaluating the functional significance of the KIR genes and their associations with specific diseases.     

The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated

Killer-cell Ig-like receptors (KIR) are structurally and functionally diverse, and enable human NK cells to survey the expression of individual HLA class I molecules, often altered in infections and tumors. Multiple events of non-reciprocal recombination have contributed to the rapid diversification of KIR. We show that approximately 4.5% of the individuals of a Caucasoid population bear a recombinant allele of KIR3DP1, officially designed KIR3DP1*004, that associates tightly with gene duplications of KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1. The KIR3DP1 gene is normally silent, but the recombinant allele carries a novel promoter sequence and, as a consequence, is transcribed in all tested individuals. Messenger RNA of KIR3DP1*004 is made up of six exons; of these, exons 1-5 are similar to, and spliced like, those encoding the leader peptide and Ig-domains of KIR3D. By contrast, exon 6 is homologous to no other human KIR sequence, but only to possible homologs in chimpanzees and rhesus macaques, and encodes a short hydrophilic tail. The putative KIR3DP1*004 product, like those of the related genes LAIR-2 and LILRA3/ILT6/LIR4, is predicted to be secreted to the extracellular medium rather than anchored to the cell membrane.     

Distribution of killer-cell immunoglobulin-like receptor genes in Eastern mainland Chinese Han and Taiwanese Han populations

The interaction between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules expressed on target cells is known to modulate the cytolytic activity of natural killer (NK) cells. To date, a wide range of KIR genotypes has been observed, which varies among different ethnic populations. We report here comparison of the KIR gene content and genotypic structure of KIRs in 106 individuals from Eastern mainland Chinese Han and 97 from Taiwanese Han. All 17 KIR genes were observed in the two populations. Framework genes 2DL4, 3DL2, 3DL3 and 3DP1 were present in all individuals. The two populations had very similar frequencies in most loci, however, significant differences were noted in the frequencies of KIR3DS1 and KIR2DS4D ( KIR2DS4 deletant variant). A total of 35 and 29 genotypes were identified in the individuals from the Eastern mainland Chinese and the Taiwanese Hans, respectively. Some pairs of KIRs showed significant positive and negative linkage disequilibrium (LD). Our data showed that there were minor distinctions in KIR gene frequencies, genotypes and LD between the two populations, which shed light on a possible geographic genetic demarcation among different Chinese communities.     

Study of the KIR gene profiles and analysis of the phylogenetic relationships of Rajbanshi population of West Bengal,India

The natural killer (NK) cells have distinct receptors called killer cell immunoglobulin-like receptors (KIR) which are responsible for regulating NK cell responses to infections and malignancy. The extensive variations in the number and type of KIR genes can be used as a tool to understand the differentiation of populations and also for tracing genetic background. In this study, we have aimed to analyze the KIR gene polymorphism in the Rajbanshi population of West Bengal, India. To our knowledge this is the first report on the KIR gene polymorphism in the Rajbanshis, a population widely distributed in the Terai and Dooars region of West Bengal, India. Herein, we have studied the gene distribution of 14 KIR genes (KIR3DL1–3DL3, KIR 2DL1–2DL5, 2DS1–2DS5 and 3DS1) and two pseudogenes (KIR3DP1 and 2DP1). The gene frequencies and genotypic frequencies were calculated, based on which statistical analyses were performed. The presence of a considerable number of genotypic profiles suggests substantial diversity in the KIR gene pool of the Rajbanshis in the region studied. Apart from the framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1) present in all the individuals, the gene frequencies of other KIR genes varied between 0.84 and 0.15. Moreover the KIR polymorphisms of the Rajbanshis were also compared with that of available published data of the populations of other ethnicities. Though the Rajbanshi population showed a tendency to cluster with other Indian population based on KIR gene frequencies, the influence of Tibeto–Burman Lineage on their KIR genotypic profiles cannot be overlooked. Furthermore, evidences from previously published data on Y chromosome haplogroup diversity study on Rajbanshis support the view. Our results will not only help to understand the genetic background of the Rajbanshi population, but also in tracing the population migration events in the North–Eastern part of India and in illustrating the extensive genetic admixture amongst the different linguistic groups of the country and also in KIR-related disease researches.     

Distribution of KIR genes in the Czech population

Killer cells immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed mainly by natural killer (NK) cells and few subsets of T lymphocytes. KIRs regulate NK cells' activity through interactions with specific HLA class I molecules and other yet unknown ligands presented on target cells. At present, 17 KIR genes and pseudogenes have been identified. As the number of KIR genes in different haplotypes varies, a wide range of genotypes in different ethnic populations may be observed. In our study, 125 healthy non-related Czech individuals were KIR typed both by sequence-specific primers and by sequence-specific oligonucleotide KIR genotyping methods. Thirty-eight different genotypes were observed in the Czech population and all 16 KIR genes known to date were found. Framework genes KIR 3DL3, KIR 2DL4, KIR 3DL2 and the pseudogene KIR 3DP1 were present in all individuals. The most frequent non-framework KIR genes detected in the Czech population were: KIR 2DL1 (95%), KIR 3DL1 (94%), KIR 2DS4 (92%) and the pseudogene 2DP1 (94%). Human leucocyte antigen (HLA)-C typing demonstrated prevalence of the C1/C2 heterozygosity (43%) and C1 homozygosity (41%) over the C2 heterozygosity. One hundred and twenty individuals from our panel carried at least one inhibitory KIR for the corresponding HLA-C group found in the genotype. Gene frequencies and found genotypes demonstrated similarity of the Czech population's KIR repertoire with the KIR repertoires of other Caucasian populations studied before.     

中国新疆地区维吾尔族人群杀伤细胞免疫球蛋白样受体基因多态性研究

背景：研究发现,杀伤细胞免疫球蛋白样受体基因具有遗传多态性,不同个体和NK细胞克隆表达不同的杀伤细胞免疫球蛋白样受体库。 目的：分析新疆维吾尔族人群杀伤细胞免疫球蛋白样受体基因多态性及基因型和单倍型特点。 方法：采用序列特异性引物PCR方法检测84名新疆维吾尔族志愿者杀伤细胞免疫球蛋白样受体基因频率,采用Hsu等的标准进行基因型和单倍型分析。 结果与结论：①共检测已知的16个杀伤细胞免疫球蛋白样受体基因,其中3DL3、2DL4、3DL2基因存在于所有个体;2DL1、3DP1、2DP1、2DL3基因较为常见;其次为2DS4、3DL1、2DL5、2DS2、2DL2、2DS1、 2DS5、3DS1;而2DS3基因频率最低。②共检测19种基因型,其中以 AJ(2,2)、AH(5,2) 和M(2,8)型较常见,频率分别为25.00%,10.71%和10.71%,其次为P(2,17)、AI(1,5)、H(2,4)和C(5,3),频率为9.52%,5.95%。5.95%和4.76%;比对发现U(17,21)、T(8,8)基因型共4例在国内文献汉族人群中未见报道。③共检出11种单倍型,最常见单倍型2占48.7%,其次是单倍型5,占15.8%;另外,发现有3种新基因型,且无法根据现有相关文献标准进行单倍型分析。表明新疆维吾尔族人群具有其独特的杀伤细胞免疫球蛋白样受体基因频率、基因型频率和单倍型频率分布,并有可能存在新的基因型和单倍型。     

KIR及HLA-A、B基因多态性与急性淋巴细胞白血病的相关性

目的探讨急性淋巴细胞白血病患者的杀伤细胞免疫球蛋白样受体（killer cell immunoglobulin-like receptors,KIR）和人类白细胞抗原（human leukocyte antigen,HLA）HLA-A、B等位基因多态性。方法采用Luminex流式技术-序列特异性寡核苷酸探针反向杂交（flow cytometry-sequence specific oligonucleotide probe,FLOW-SSOP）方法对内蒙地区48例急性淋巴细胞白血病患者HLA-A、B等位基因多态性进行分析,PCR-SSP技术进行KIR抑制基因的低分辨率检测。以北方地区健康群体资料作为正常对照。结果 （1）在急性淋巴细胞白血病中HLA-A＊31XX,A＊6901等位基因频率高于对照组（1.955%,0.071%）,差异有统计学意义（P〈0.05）;A＊33XX等位基因频率低于对照组（5.825%）,差异有统计意义（P〈0.05）;（2）在HLA-B等位基因中,急性淋巴细胞白血病B＊07XX,＊27XX,＊38XX,＊41XX,＊49XX,＊59XX等位基因频率高于对照组（2.069%,0.968%,0.702%,0.091%,0.051%,0.061%）,差异有统计学意义（P〈0.05）;其中HLA-B＊59XX的相对危险度高（RR=35.156）,其它等位基因频率在两组之间无显著性差异。在急性白血病患者中,高频率KIR基因有KIR3DP1,2DP1,2DL1,2DL3,3DL1、2DL5,2DS4及3DS1。急性白血病组3DL1基因型频率比对照组的显著降低。结论 HLA-A＊31XX,A＊6901;B＊07XX,B＊27XX,B＊38XX,B＊41XX,B＊49XX,B＊59XX;等位基因与ALL相关联,有遗传易感作用。HLA-B＊59XX等位基因携带者,可能患ALL的危险度增高（RR=35.156）KIR3DL1和2DS4均与ALL呈关联。     

江苏汉族人群杀伤细胞免疫球蛋白样受体及其特异性配体HLA分析

目的:分析杀伤细胞免疫球蛋白样受体(KIR)及其特异性配体HLAⅠ类分子在江苏地区汉族人群的分布特点。方法:分别利用real-time PCR法和PCR-SSP方法对173例无血缘关系的江苏汉族健康人群进行KIR和HLA-Cw,HLA-Bw4分型,并分析KIR/HLA配对组合的类型和数量。结果:江苏汉族人群中,>92%的个体同时表达四种抑制性KIR(iKIR)(2DL1,2DL2/3,3DL1,3DL2)。2DL2/HLA-C1,2DL3/HLA-C1,2DL1/HLA-C2,3DL1/Bw4的频率分别依次分别为0.243,0.971,0.457,0.590;2DS1/HLA-C2,2DS2/HLA-C1的频率为0.162,0.231。54.3%的个体只表达2DL1而不表达相应的配体HLA-C2,32.9%的个体只表达3DL1而缺乏配体HLA-Bw4,另有5.8%的个体只表达HLA-Bw4而不表达3DL1。27.7%的个体同时表达3种iKIR/HLA,26%的个体同时表达两种iKIR/HLA,25.4%的个体只遗传一个iKIR/HLA配对,未发现3种iKIR/HLA同时缺失的个体。结论:在江苏汉族人群中,存在KIR与HLA表型分离现象,抑制性KIR/HLA配对表达高于刺激性KIR/HLA配对,约1/4个体只表达单个iKIR/HLA配对。     

尿毒症患者NK1细胞表面受体KIR基因的表达

目的 调查人类自然杀伤(NK)细胞表面免疫球蛋白样受体KIR在尿毒症患者的表达.方法 采用PCR-SSP完成55例尿毒症患者KIR基因分析.结果 尿毒症患者表达16个KIR基因,2DL4、3DL2、3DL3、3DPI基因频率1.00,2DL1、2DL3、3DL1、2DS4基因频率0.73～0.87,2DL2、2DS1、2DS2、2DS3、2DS5基因频率0.11～025,2DL5、3DS1、2DP1基因频率0.30～0.41.对尿毒症患者与部分亚洲地区人群的分布频率比较分析中发现,KIR-2DL4、3DL1、3DL2,3DL3、2DS4(GF 0.73～1.00)和KIR-2DL2、2DL5、2DS1、2DS3、2DS5、3DS1(GF0.11～0.34)与韩国人、日本人、南亚人之间相差＜0.20;KIR-2DL1、2DL3、2DS2与韩国人、日本人、南亚人群之间相差≥0.20,2DL1低于日本人,2DS2低于南亚人,2DL3高于南亚人.结论 55例尿毒症患者普遍带有结构基因2DL4、3DL2、3DL3、3DP1,其次为2DL1、2DL3、3DL1、2DS4,较罕见为2DL2、2DS1、2DS2、2DS3和2DS5;显示尿毒症患者中14个KIR功能基因频率与亚洲其他人群KIR基因频率接近,但是KIR基因多态性与上述不同种族之间存在分布差异.     

Real-time PCR分型法检测苏南地区汉族人群KIR基因多态性

目的利用SYBR Green I Real-time PCR分型方法检测杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-likereceptor,KIR)基因,探讨苏南地区汉族人群KIR基因的分布特点。方法应用SYBR Green I Real-time PCR法对191名苏南地区汉族非亲缘健康人群进行KIR基因分型。结果 SYBR Green I Real-time PCR法有效地进行了KIR基因分型。已知的16种KIR基因在苏南地区汉族人群均被检出。框架基因2DL4、3DL2、3DL3和假基因3DP1存在于所有受检个体中。最常见的非框架基因为2DL1、2DL3、3DL1、2DS4以及假基因2DP1。共检出33种KIR基因型,最常见的为AA1(39.27%),其次为BX2、BX4和BX8。发现仅在新加坡华人报道的罕见基因型BX331和BX337,及仅在墨西哥人群罕见的基因型BX427。结论苏南汉族人群中检测出已知的16种KIR基因,共发现33种基因型,最常见的为AA1,并见到3个罕见基因型BX331、BX337和BX427。     

Discrimination between the main activating and inhibitory killer cell immunoglobulin-like receptor positive natural killer cell subsets using newly characterized monoclonal antibodies

Natural killer (NK) cells are key components of the innate anti-viral and anti-tumour immune responses. NK cell function is regulated by the interaction of killer cell immunoglobulin-like receptors (KIR) with human leucocyte antigen (HLA) class I molecules. In this study, we report on the generation of KIR-specific antibodies allowing for discrimination between activating and inhibitory KIR. For this purpose, BALB/c mice were immunized with human KIR2DS2 recombinant protein. The precise specificity of KIR2DS2-specific clones was determined on KIR-transfected BW cells and KIR-genotyped NK cells. When used in combination with EB6 (KIR2DL1/2DS1) or GL183 (KIR2DL2/2DL3/2DS2), two KIR-specific monoclonal antibodies (mAbs), 8C11 (specific for KIR2DL1/2DL2/2DL3/2DS2) and 1F12 (specific for KIR2DL3/2DS2), discriminated activating KIR2DS1 (8C11⁻ EB6⁺) from inhibitory KIR2DL1 (8C11⁺ GL183⁻) and KIR2DL2 (1F12⁻ GL183⁺), while excluding the main HLA-Cw-specific KIR. Using these mAbs, KIR2DS1 was shown to be expressed on the surface of NK cells from all individuals genotyped as KIR2DS1⁺ (n = 23). Moreover, KIR2DS1 and KIR2DL1 were independently expressed on NK cells. We also determined the amino acid position recognized by the 8C11 and 1F12 mAbs, which revealed that some KIR2DL1 allele-encoded proteins are not recognized by 8C11. Because most available anti-KIR mAbs recognize both inhibitory and activating forms of KIR, these newly characterized antibodies should help assess the expression of activating and inhibitory KIR and their functional relevance to NK biology.