BACKGROUND: The mammalian Leukocyte Receptor Complex (LRC) chromosomal region may contain gene families for the killer cell immunoglobulin-like receptor (KIR) and/or leukocyte immunoglobulin-like receptor (LILR) collections as well as various framing genes. This complex region is well described in humans, mice, and some domestic animals. Although single KIR genes are known in some Carnivora, their complements of LILR genes remain largely unknown due to obstacles in the assembly of regions of high homology in short-read based genomes. METHODS: As part of the analysis of felid immunogenomes, this study focuses on the search for LRC genes in reference genomes and the annotation of LILR genes in Felidae. Chromosome-level genomes based on single-molecule long-read sequencing were preferentially sought and compared to representatives of the Carnivora. RESULTS: Seven putatively functional LILR genes were found across the Felidae and in the Californian sea lion, four to five genes in Canidae, and four to nine genes in Mustelidae. They form two lineages, as seen in the Bovidae. The ratio of functional genes for activating LILRs to inhibitory LILRs is slightly in favor of inhibitory genes in the Felidae and the Canidae; the reverse is seen in the Californian sea lion. This ratio is even in all of the Mustelidae except the Eurasian otter, which has a predominance of activating LILRs. Various numbers of LILR pseudogenes were identified. CONCLUSIONS: The structure of the LRC is rather conservative in felids and the other Carnivora studied. The LILR sub-region is conserved within the Felidae and has slight differences in the Canidae, but it has taken various evolutionary paths in the Mustelidae. Overall, the process of pseudogenization of LILR genes seems to be more frequent for activating receptors. Phylogenetic analysis found no direct orthologues across the Carnivora which corroborate the rapid evolution of LILRs seen in mammals.
- MeSH
- Canidae * MeSH
- Carnivora * genetika MeSH
- Felidae * MeSH
- fylogeneze MeSH
- genomika MeSH
- lachtani * MeSH
- leukocyty MeSH
- lidé MeSH
- Mustelidae * MeSH
- myši MeSH
- receptory imunologické genetika MeSH
- receptory KIR genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
NK buňky hrají u alogenní transplantace kostní dřeně významnou roli, nejen při eradikaci zbývajících nádorových buněk, ale ovlivňují i rozvoj reakce štěpu proti hostiteli. Je tedy třeba porozumět jejich regulaci a tomu, jakým způsobem může reakce imunitního systému pacienta NK buňky dárce ovlivňovat. Inhibice a aktivace NK buněk je řízena celou řadou receptorů, které reagují na široké spektrum ligandů. Ať už inhibičních, které signalizují NK buňkám, že je cílová buňka v pořádku nebo aktivačních, které vyjadřují nějaké poškození cílové buňky. Mezi nejprozkoumanější receptory patří KIR a dále NKG2D se svými ligandy MICA a MICB. Přehledu jejich role v transplantaci kostní dřeně se věnuje tato práce.
NK cells play an important role in allogeneic stem cell transplantation; not only as effector cells in the eradication of remaining cancer cells but also as potential inducers of graft versus host disease. Hence, it is important to understand their regulation and how the patient’s immune system affects donor NK cells. NK cell inhibition or activation is directed by many receptors which interact with a broad spectrum of ligands. Inhibition ligands signal that the target cell is healthy, and activating ligands reflect that the cell is damaged. The most investigated receptors are KIR together with the NKG2D receptor with its ligands MICA and MICB. This work describes their role in stem cell transplantation.
- MeSH
- akutní myeloidní leukemie * imunologie terapie MeSH
- haplotypy genetika MeSH
- HLA antigeny MeSH
- homologní transplantace MeSH
- lektinové receptory NK-buněk - podrodina K analýza genetika MeSH
- lidé MeSH
- ligandy MeSH
- polymorfismus genetický MeSH
- receptory buněk NK * imunologie klasifikace MeSH
- receptory KIR analýza genetika MeSH
- transplantace kostní dřeně MeSH
- transplantační imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Hepatitis B virus (HBV) infection is one of the most common infections worldwide, having negative impact on world health due to the tendency for chronification with late complications such as liver cirrhosis and hepatocellular carcinoma. Natural killer (NK) cells as part of innate antiviral defense influence the clinical course of HBV infection: elimination of the virus or chronic disease. AIM: Therefore, we investigated the polymorphisms of the main gene systems, regulating NK-cell function: killer cell immunoglobulin-like receptors (KIRs) and their appropriate HLA class I ligands in 144 HBV infected patients (124 chronic carriers and 20 spontaneously recoved) and 126 ethnically matched healthy controls from the Bulgarian population in a case-control study. METHODS: KIRs and HLA ligands were determined by PCR-SSP or PCR high-resolution typing methods. RESULTS: KIR2DL5B allele variant was significantly less frequent in spontaneously recovered (SR) patients compared to healthy controls (10.0% vs. 45.5%, Pcorr=0.006). The presence of KIR3DL1*004 allele was higher in chronic HBV carriers (CH) than in controls (33.1% vs. 17.6%, Pcorr=0.036). Additionally, SR patients differed from healthy individuals by the lower frequency of HLA-Bw4Ile80 group ligands (30.0% vs 63.7%, P=0.015). Three KIR genotypes were found more frequent in healthy in comparison with HBV infected individuals: ID2 (13.5% vs 5.6%, P=0.025), KIR genotype containing 6 activating KIRs (18.0% vs 7.6%, P=0.017), and KIR genotype composed of 4 activating and 5 inhibitory KIRs (23.8% vs 5.6%, P=0.001). CONCLUSION: These data suggest that inherited KIR and HLA class I ligand polymorphisms may influence the clinical course of HBV infection.
Předmětem naší práce je analýza vlivu imunologických parametrů s cílem optimalizace rutinního výběru nepříbuzných dárců krvetvorných buněk. Základním požadavkem úspěšnosti transplantace je shoda mezi dárcem a příjemcem v HLA systému I. a II. třídy. Využití genetických metod pro určení shody v HLA I. třídy znamenalo v našem souboru zlepšení přežití transplantovaných pacientů. Další zpřesnění genetických metod ale již žádné významné zlepšení nepřineslo. U souboru 240 dárců byla sledována míra shody v HLA-DPB1, pouze 8,2 % z nich bylo shodných se svými pacienty. Dalších 114 dárců mělo neshody tolerovatelné dle klinického prognostického modelu DPB1 T-Cell Epitope Algorithm. Netolerovatelné neshody byly detekovány u 37 % dárců. KIR genotyp, který ovlivňuje potransplantační průběh především u pacientů s akutní myeloidní leukemií (AML), byl testován u 347 dárců, 70 % bylo zařazeno do kategorie „neutrální“, 19,3 % bylo v kategorii „lepší“ a 10, 7 % v kategorii „nejlepší“ dle Donor KIR B-content group calculator. Zastoupení jednotlivých kategorií se nelišilo mezi skupinou neselektovaných dárců a dárců vybraných pro transplantaci pro pacienty s AML. Do rutinního výběru dárců bylo zařazeno vyhledání dle tolerovatelnosti neshod v HLA-DPB1, kategorie KIR jsou pouze doplňkovým parametrem aktuálního algoritmu výběru dárců.
The aim of our work was to analyse the influence of immunological parameters in order to optimize routine selection of unrelated stem cell donors. Match in HLA class I and II between the donor and the recipient is the essential requirement for success of the transplantation. The use of genetic methods for match determination in HLA class I improved survival of transplanted patients in our cohort. Further refinement of genetic methods has not resulted in any significant improvement. In a group of 240 donors, the match rate in HLA-DPB1 was monitored, only 8.2% were comletely matched with their patients. Another 114 donors had mismatches tolerable in the DPB1 T-Cell Epitope Algorithm clinical prognostic model. Intolerable mismatches were detected in 37% of donors. The KIR genotype, which affects the post-transplantation course especially in patients with acute myeloid leukemia (AML), was tested in 347 donors, 70% were classified as “neutral”, 19.3% were in “better” and 10.7% in “best” category by Donor KIR B-content group calculator. The representation of individual categories did not differ between the group of non-selected donors and donors selected for transplantation for patients with AML. Routine selection of donors included a search according to the tolerability of mismatches in HLA-DPB1, KIR categories are only a supplementary parameter of the current donor selection algorithm.
- MeSH
- HLA antigeny genetika imunologie MeSH
- lidé MeSH
- nepříbuzný dárce MeSH
- prospektivní studie MeSH
- receptory KIR genetika imunologie MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výběr dárců * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Despite the independent segregation of genes encoding killer immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA), there is some evidence of some kind of co-evolution. Therefore, one could expect reduced KIR diversity within the HLA restricted population. A total of 41 unrelated individuals homozygous for ancestral HLA haplotype AH8.1 (HLA-A*0101-Cw*0701-B*0801-DRB1*0301-DQB1*0201) were genotyped for KIRs. Over all, 14 different genotypes were identified. The KIR genes and genotypes repertoire generally mirror the published frequencies in Caucasians. Except for KIR2DS4, all activating genes presented frequencies below 50%. KIR2DS5 was the least frequent among activating genes (17%), whereas KIR2DL5 (37%) among inhibitory ones. The most frequent (39%) was AA genotype. Twenty-two individuals (54%) had a copy of KIR haplotypes A and B (AB genotype), whereas three (7%) were homozygous for B (BB genotype). Nine of fourteen reported genotypes occurred only in one individual. Five genotypes were reported in less than twenty individuals worldwide and one genotype was reported so far only once. Conversely, the three most frequent genotypes account for 68% of all detected genotypes. The results show the unrestricted KIR diversity in this HLA uniform group and support the fact that the driving force for KIR evolution is not exclusively a major histocompatibility complex.
- MeSH
- DNA analýza genetika MeSH
- frekvence genu MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- HLA antigeny genetika MeSH
- homozygot MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- populační skupiny genetika MeSH
- receptory KIR genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- běloši genetika MeSH
- financování organizované MeSH
- frekvence genu MeSH
- lidé MeSH
- pseudogeny MeSH
- receptory KIR genetika MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
