title: Compound KIR-HLA genotype analyses in the Iranian population by a novel PCR-SSP assay.
abstract: Natural killer (NK) cells eliminate infected and transformed cells while still are self-tolerant. Interactions of the independently segregating Killer cell immunoglobulin-like receptors (KIR) and human leucocyte antigens (HLA) loci play a critical role in NK cell regulation. Different compound KIR-HLA genotypes can impart different thresholds of activation to the NK-cell repertoire and such genotypic variation has been found to confer altered risk in a number of human diseases including viral infections, autoimmune disorders, reproduction abnormalities and cancers. In this study, we presented a novel combined KIR-HLA polymerase chain reaction-sequence-specific primers genotyping assay for simultaneous determination of KIR genes and their three major HLA class I ligand groups (C1, C2, and Bw4). Moreover, known inhibitory and activating KIR + HLA (iKIR + HLA: 2DL2/3 + C1, 2DL1 + C2, 3DL1 + Bw4; and aKIR + HLA: 2DS2 + C1, 2DS1 + C2, 3DS1 + Bw4) combinations as well as co-inheritance of aKIR genes and iKIR + HLA pairs were analysed in a total of 200 unrelated healthy Iranian individuals. All tested subjects had at least one of the three iKIR + HLA pairs and the frequencies of various inhibitory combinations in the study group were: 31.5%, three iKIR + HLA pairs, 53.5%, two iKIR + HLA pairs, and 15%, 0ne iKIR + HLA pair. Furthermore, we revealed that majority of Iranians (69%) carry compound genotypes with greater number of inhibitory pairings than activating combinations (iKIR + HLA > aKIR + HLA). Conversely, iKIR + HLA < aKIR (45%) was dominant genotype in the study group. We conclude that selective evolutionary pressure has propensity to maintain KIR-HLA genotypes with more inhibitory combinations to guarantee self-tolerance. In contrast, existence of activating KIR genes without normal endogenous ligands, potentially arms the NK population for competent immunosurveillance and stronger defense against infections.
authors.affiliation: Division of Transplant Immunology and Immunogenetics, Department of Immunology, Iran University of Medical Sciences, Tehran, Iran. nadertajik@iums.ac.ir
authors.forename: N
authors.initials: N
authors.lastname: Tajik
authors.forename: F
authors.initials: F
authors.lastname: Shahsavar
authors.forename: M
authors.initials: M
authors.lastname: Nasiri
authors.forename: M F
authors.initials: MF
authors.lastname: Radjabzadeh
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007492:Iran; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D054340:Receptors, KIR