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Killer Cell Immunoglobulin-Like Receptor (KIR) Genes    and Association with  Human Viral Infections                 Mirko...
At a glance ...• Natural killer cells•   Leukocyte Receptor Complex•   KIR genes•   KIR genes diversity•   Determination o...
A model for natural T cells role  within the immune system                         3
Natural killer (NK) cells and cytotoxic T cells (CTL) are professional killer cells and share several common featuresbut d...
The extended   Leukocyte   Receptor    Complex(19q13.4) and a KIR haplotype                  5
KIR gene organisation                  6
KIR protein structures                   7
Approximate KIR proteindomain and region lengths                    8
KIR Gene Names Gene      Protein                                  Description                                             ...
KIR Allele Nomenclature                   10
Determination of KIR genes bysingle strand polymorphism (SSP)              method                        11
Identification of KIR genes by SSP               method                          12
KIR gene frequencies inMacedonian population                    13
KIR genotypesin Macedonianpopulation (n =     214)                  14
France                                                   Argentina                                                   Irela...
Interaction between KIR genes and          their ligand (HLA)                         16
Killer cell immunoglobulin-like receptor(KIR) diversity can impact natural killer       (NK) cells at different levels    ...
Natural killer (NK) cells are diverse at the level of receptors, ligands and         signalling adaptors                  ...
Diversity of KIR genes and their ligandsheredited in offspring from the parents with   different KIR and HLA genotypes ......
... Diversity of KIR genes and their ligandsheredited in offspring from the parents with   different KIR and HLA genotypes...
KIR3DL1/S1,  like HLA-A,    B, C and  HLA-DRB1, is one of the  most highly polymorphichuman genes                 21
Association of KIR with viruses•   HIV-1•   HCV•   HBV•   (H1N1)pdm90•   West Nile Virus                           22
Model for the engagement of NK cells to mediate HIV inhibition                         23
NK cell-mediated recognition of     HIV-1 infected cells                        24
KIR3DL1 polymorphism affects   specificity for HLA class I                       25
KIR gene frequencies in control and patients   with chronic hepatitis C viral infection                                 26
Combined effect HLA-C1C1/Bw4-80/(KIR2DS4/1D) on hepatocellular carcinoma(HCC) occurrence in HBV-infected patients         ...
Comparison of KIR3DL1/S1 allele frequencies between (H1N1)pdm09 ICUpatients and analogous world populations               ...
Percentages of carriers of inhibitory, activating, and  pseudogene KIR genes in a control Gabonese population and in conta...
Comparison of the observed and estimated KIRgene frequencies for critically ill Macedonian patients with pandemic influenz...
KIR locus haplogroups, genotypes ID and genotype  frequency of critically ill Macedonian patients with pandemic influenza ...
Comparison of the observed and estimated KIR    gene frequencies for Macedonian patients with     West Nile Virus (WNV) in...
KIR genotype frequencies in Macedonianpatients with West Nile Virus (WNV) infection(N = 4) and healthy Macedonians (N=214)...
Conclusions• Associations of KIR genes, alleles,  genotypes and haplotypes are found with  some viral infections (HIV-1, H...
AcknowledgementAssociate Professor Dr. Dejan TrajkovAssistant Dr. Aleksandar PetlichkovskiAssistant Dr. Slavica Hristomano...
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Killer Cell Immunoglobulin-Like Receptor (KIR) Genes and Association with Human Viral Infections

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Associations of KIR genes, alleles, genotypes and haplotypes are found with some viral infections (HIV-1, HCV, HBV, (H1N1)pdm09, Ebola, and WNV).

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Killer Cell Immunoglobulin-Like Receptor (KIR) Genes and Association with Human Viral Infections

  1. 1. Killer Cell Immunoglobulin-Like Receptor (KIR) Genes and Association with Human Viral Infections Mirko Spiroski, MD, PhDInstitute of Immunobiology and Human Genetics, Faculty of Medicine,University "Ss. Cyril and Methodius", Skopje, Republic of Macedonia http://www.iibhg.ukim.edu.mk/ e-mail: mspiroski@yahoo.com FB: mirko.spiroski
  2. 2. At a glance ...• Natural killer cells• Leukocyte Receptor Complex• KIR genes• KIR genes diversity• Determination of KIR genes• Diversity of KIR genes• Association of KIR genes with viruses 2
  3. 3. A model for natural T cells role within the immune system 3
  4. 4. Natural killer (NK) cells and cytotoxic T cells (CTL) are professional killer cells and share several common featuresbut differ by their HLA class I-specific receptors that are used to distinguish unhealthy targets from the healthy host cells 4
  5. 5. The extended Leukocyte Receptor Complex(19q13.4) and a KIR haplotype 5
  6. 6. KIR gene organisation 6
  7. 7. KIR protein structures 7
  8. 8. Approximate KIR proteindomain and region lengths 8
  9. 9. KIR Gene Names Gene Protein Description AliasesSymbol SymbolKIR2DL1 KIR2DL1 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 1 47.11, CD158a, cl-42, nkat1, p58.1KIR2DL2 KIR2DL2 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2 CD158b1, cl-43, nkat6KIR2DL3 KIR2DL3 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3 CD158b2, cl-6, nkat2, nkat2a, nkat2b, p58KIR2DL4 KIR2DL4 killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 4 15.212, 103AS, CD158dKIR2DL5A KIR2DL5A killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 5A CD158f, KIR2DL5.1KIR2DL5B KIR2DL5B killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 5B KIR2DL5.2, KIR2DL5.3, KIR2DL5.4KIR2DS1 KIR2DS1 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1 CD158h, EB6Actl, EB6ActllKIR2DS2 KIR2DS2 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 2 183Actl, CD158j, cl-49, nkat5KIR2DS3 KIR2DS3 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 3 nkat7KIR2DS4 KIR2DS4 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 4 CD158i, cl-39, KKA3, nkat8KIR2DS5 KIR2DS5 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 5 CD158g, nkat9KIR2DP1 KIR2DP1 killer cell immunoglobulin-like receptor, two domains, pseudogene 1 KIR2DL6, KIR15, KIRY, KIRZKIR3DL1 KIR3DL1 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1 AMB11, CD158e1, cl-2, cl-11, KIR, nkat3, NKB1, NKB1BKIR3DL2 KIR3DL2 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 CD158k, cl-5, nkat4, nkat4a, nkat4bKIR3DL3 KIR3DL3 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 3 CD158z, KIR3DL7, KIR44, KIRC1KIR3DS1 KIR3DS1 killer cell immunoglobulin-like receptor, three domains, short cytoplasmic tail, 1 CD158e2, nkat10KIR3DP1 KIR3DP1 killer cell immunoglobulin-like receptor, three domains, pseudogene, 1 CD158c, KIR2DS6, KIR3DS2P, KIR48, KIRX 9
  10. 10. KIR Allele Nomenclature 10
  11. 11. Determination of KIR genes bysingle strand polymorphism (SSP) method 11
  12. 12. Identification of KIR genes by SSP method 12
  13. 13. KIR gene frequencies inMacedonian population 13
  14. 14. KIR genotypesin Macedonianpopulation (n = 214) 14
  15. 15. France Argentina IrelandNorthern Italy BelgiumKIRPopKIR genetic Lebanon Reunion SwedenVasterbottenthree of 29 Macedonia SpainGranada world MexicoVeraCruzMestizos EnglandWestMidlandsCaucasian EnglandWestMidlandsIndianAsianpopulations Basque Africans EnglandWestMidlandsAfroCaribbean Guadeloupe Senegal Koreans Japanese Finland Mestizo Tarahumara Huichol Purepecha IndiaNorthHindus SouthAsians PakistanKarachi BrazilSouthEastCaucasian 0.020 0.015 0.010 0.005 150.000
  16. 16. Interaction between KIR genes and their ligand (HLA) 16
  17. 17. Killer cell immunoglobulin-like receptor(KIR) diversity can impact natural killer (NK) cells at different levels 17
  18. 18. Natural killer (NK) cells are diverse at the level of receptors, ligands and signalling adaptors 18
  19. 19. Diversity of KIR genes and their ligandsheredited in offspring from the parents with different KIR and HLA genotypes ... 19
  20. 20. ... Diversity of KIR genes and their ligandsheredited in offspring from the parents with different KIR and HLA genotypes ... 20
  21. 21. KIR3DL1/S1, like HLA-A, B, C and HLA-DRB1, is one of the most highly polymorphichuman genes 21
  22. 22. Association of KIR with viruses• HIV-1• HCV• HBV• (H1N1)pdm90• West Nile Virus 22
  23. 23. Model for the engagement of NK cells to mediate HIV inhibition 23
  24. 24. NK cell-mediated recognition of HIV-1 infected cells 24
  25. 25. KIR3DL1 polymorphism affects specificity for HLA class I 25
  26. 26. KIR gene frequencies in control and patients with chronic hepatitis C viral infection 26
  27. 27. Combined effect HLA-C1C1/Bw4-80/(KIR2DS4/1D) on hepatocellular carcinoma(HCC) occurrence in HBV-infected patients 27
  28. 28. Comparison of KIR3DL1/S1 allele frequencies between (H1N1)pdm09 ICUpatients and analogous world populations 28
  29. 29. Percentages of carriers of inhibitory, activating, and pseudogene KIR genes in a control Gabonese population and in contacts (IgG+), survivors, and fatalities of Ebola virus infection 29
  30. 30. Comparison of the observed and estimated KIRgene frequencies for critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection (N = 63) and healthy Macedonians (N=214)N, number of individuals; F, observed frequency was obtained by direct counting; GF, genefrequencies were calculated using the formula GF=1-√(1-F); p, statistical significance; &,cannot be calculated because expected <5, χ2 test; OR, Odds ratio; CI,confidence interval. 30
  31. 31. KIR locus haplogroups, genotypes ID and genotype frequency of critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection (N = 63) and corresponding frequencies in healthy Macedonians (n=214)KIR Genotype [1=Positive, 0=negative] 31
  32. 32. Comparison of the observed and estimated KIR gene frequencies for Macedonian patients with West Nile Virus (WNV) infection (N = 4) and healthy Macedonians (N=214)N, number of individuals; F, observed frequency was obtained by direct counting; GF, genefrequencies were calculated using the formula GF=1-(1-F); p, statistical significance; &, cannot becalculated because expected <5, 2 test; OR, Odds ratio; CI, confidence interval. 32
  33. 33. KIR genotype frequencies in Macedonianpatients with West Nile Virus (WNV) infection(N = 4) and healthy Macedonians (N=214) N, number of individuals displaying certain Bx KIR genotype; F, frequency of KIR genotype; CI, confidence interval. &, cannot be calculated. 33
  34. 34. Conclusions• Associations of KIR genes, alleles, genotypes and haplotypes are found with some viral infections (HIV-1, HCV, HBV, (H1N1)pdm09, Ebola, and WNV).• We expect intensive investigations about the susceptibility and/or resistance to viral infections connected with KIR genes and their ligands. 34
  35. 35. AcknowledgementAssociate Professor Dr. Dejan TrajkovAssistant Dr. Aleksandar PetlichkovskiAssistant Dr. Slavica HristomanovaAssistant Dr. Meri KirijasAssistant Dr. Aleksandar SenevBiotechnologist Olivija Efinska-MladenovskaMolecular biolog Olgica SibinovskaLaboratory technician Elena Cvetkovska 35

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