Advertisement

Natural Killer Cells and Killer-Cell Immunoglobulin-Like Receptor Polymorphisms: Their Role in Hematopoietic Stem Cell Transplantation

  • Jennifer Schellekens
  • Katia Gagne
  • Steven G. E. Marsh
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1109)

Abstract

Natural killer (NK) cells are important effector cells in the early control of infected, malignant, and “nonself” cells. Various receptor families are involved in enabling NK cells to detect and efficiently eliminate these target cells. The killer-cell immunoglobulin-like receptor (KIR) family is a set of receptors that are very polymorphic with regard to gene content, expression level, and expression pattern. KIRs are responsible for the induction of a NK cell alloreactive response through their interaction with HLA class I molecules. The role of NK cells in hematopoietic stem cell transplantation (HSCT) has been studied for many years, and induction of antileukemic responses by donor NK cells has been reported. Conflicting data still exist on the exact circumstances in which the KIR repertoire affects and influences clinical outcome after HSCT. More large-scale studies are needed on well-defined cohorts to unravel the mechanism of action of the NK cell-mediated alloresponse in an HSCT setting.

Key words

NK cells KIR KIR genotyping KIR polymorphism HLA class I HSCT 

References

  1. 1.
    Robertson MJ, Ritz J (1990) Biology and clinical relevance of human natural killer cells. Blood 76:2421–2438PubMedGoogle Scholar
  2. 2.
    O’Leary JG, Goodarzi M, Drayton DL et al (2006) T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol 7:507–516PubMedGoogle Scholar
  3. 3.
    Paust S, von Andrian UH (2011) Natural killer cell memory. Nat Immunol 12:500–508PubMedGoogle Scholar
  4. 4.
    Vivier E, Raulet DH, Moretta A et al (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331:44–49PubMedCentralPubMedGoogle Scholar
  5. 5.
    Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201–214PubMedGoogle Scholar
  6. 6.
    Warren HS (1996) NK cell proliferation and inflammation. Immunol Cell Biol 74:473–480PubMedGoogle Scholar
  7. 7.
    Farag SS, Fehniger TA, Ruggeri L et al (2002) Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood 100:1935–1947PubMedGoogle Scholar
  8. 8.
    Karre K, Ljunggren HG, Piontek G et al (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319:675–678PubMedGoogle Scholar
  9. 9.
    Ljunggren HG, Karre K (1990) In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today 11:237–244PubMedGoogle Scholar
  10. 10.
    Kim S, Poursine-Laurent J, Truscott SM et al (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436:709–713PubMedGoogle Scholar
  11. 11.
    Ritz J, Schmidt RE, Michon J et al (1988) Characterization of functional surface structures on human natural killer cells. Adv Immunol 42:181–211PubMedGoogle Scholar
  12. 12.
    Walzer T, Jaeger S, Chaix J et al (2007) Natural killer cells: from CD3(-)NKp46(+) to post-genomics meta-analyses. Curr Opin Immunol 19:365–372PubMedGoogle Scholar
  13. 13.
    Lanier LL, Testi R, Bindl J et al (1989) Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 169:2233–2238PubMedGoogle Scholar
  14. 14.
    Yu J, Mitsui T, Wei M et al (2011) NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human. J Clin Invest 121:1456–1470PubMedCentralPubMedGoogle Scholar
  15. 15.
    Nagler A, Lanier LL, Cwirla S et al (1989) Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol 143:3183–3191PubMedGoogle Scholar
  16. 16.
    Lanier LL, Le AM, Civin CI et al (1986) The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136:4480–4486PubMedGoogle Scholar
  17. 17.
    Cooper MA, Fehniger TA, Turner SC et al (2001) Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood 97:3146–3151PubMedGoogle Scholar
  18. 18.
    Smyth MJ, Cretney E, Kelly JM et al (2005) Activation of NK cell cytotoxicity. Mol Immunol 42:501–510PubMedGoogle Scholar
  19. 19.
    Brown D, Trowsdale J, Allen R (2004) The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens 64:215–225PubMedGoogle Scholar
  20. 20.
    Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274PubMedGoogle Scholar
  21. 21.
    Borrego F, Masilamani M, Marusina AI et al (2006) The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance. Immunol Res 35:263–278PubMedGoogle Scholar
  22. 22.
    Valiante NM, Uhrberg M, Shilling HG et al (1997) Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity 7:739–751PubMedGoogle Scholar
  23. 23.
    Cheent K, Khakoo SI (2009) Natural killer cells: integrating diversity with function. Immunology 126:449–457PubMedCentralPubMedGoogle Scholar
  24. 24.
    Raulet DH, Guerra N (2009) Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol 9:568–580PubMedCentralPubMedGoogle Scholar
  25. 25.
    Trowsdale J, Barten R, Haude A et al (2001) The genomic context of natural killer receptor extended gene families. Immunol Rev 181:20–38PubMedGoogle Scholar
  26. 26.
    Barrow AD, Trowsdale J (2008) The extended human leukocyte receptor complex: diverse ways of modulating immune responses. Immunol Rev 224:98–123PubMedGoogle Scholar
  27. 27.
    Lanier LL (2009) DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev 227:150–160PubMedCentralPubMedGoogle Scholar
  28. 28.
    Faure M, Long EO (2002) KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. J Immunol 168:6208–6214PubMedGoogle Scholar
  29. 29.
    Marsh SGE, Parham P, Dupont B et al (2003) Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002. Tissue Antigens 62:79–86PubMedGoogle Scholar
  30. 30.
    Vilches C, Rajalingam R, Uhrberg M et al (2000) KIR2DL5, a novel killer-cell receptor with a D0-D2 configuration of Ig-like domains. J Immunol 164:5797–5804PubMedGoogle Scholar
  31. 31.
    Wilson MJ, Torkar M, Haude A et al (2000) Plasticity in the organization and sequences of human KIR/ILT gene families. Proc Natl Acad Sci USA 97:4778–4783PubMedCentralPubMedGoogle Scholar
  32. 32.
    Norman PJ, Stephens HA, Verity DH et al (2001) Distribution of natural killer cell immunoglobulin-like receptor sequences in three ethnic groups. Immunogenetics 52:195–205PubMedGoogle Scholar
  33. 33.
    Uhrberg M, Valiante NM, Shum BP et al (1997) Human diversity in killer cell inhibitory receptor genes. Immunity 7:753–763PubMedGoogle Scholar
  34. 34.
    Martin AM, Kulski JK, Gaudieri S et al (2004) Comparative genomic analysis, diversity and evolution of two KIR haplotypes A and B. Gene 335:121–131PubMedGoogle Scholar
  35. 35.
    Hsu KC, Chida S, Geraghty DE et al (2002) The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism. Immunol Rev 190:40–52PubMedGoogle Scholar
  36. 36.
    Martin MP, Single RM, Wilson MJ et al (2008) KIR haplotypes defined by segregation analysis in 59 Centre d’Etude Polymorphisme Humain (CEPH) families. Immunogenetics 60:767–774PubMedCentralPubMedGoogle Scholar
  37. 37.
    Maxwell LD, Wallace A, Middleton D et al (2002) A common KIR2DS4 deletion variant in the human that predicts a soluble KIR molecule analogous to the KIR1D molecule observed in the rhesus monkey. Tissue Antigens 60:254–258PubMedGoogle Scholar
  38. 38.
    Bashirova AA, Martin MP, McVicar DW et al (2006) The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense. Annu Rev Genomics Hum Genet 7:277–300PubMedGoogle Scholar
  39. 39.
    Hiby SE, Regan L, Lo W et al (2008) Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage. Hum Reprod 23:972–976PubMedGoogle Scholar
  40. 40.
    Yawata M, Yawata N, McQueen KL et al (2002) Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression. Immunogenetics 54:543–550PubMedGoogle Scholar
  41. 41.
    Toneva M, Lepage V, Lafay G et al (2001) Genomic diversity of natural killer cell receptor genes in three populations. Tissue Antigens 57:358–362PubMedGoogle Scholar
  42. 42.
    Yawata M, Yawata N, Abi-Rached L et al (2002) Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family. Crit Rev Immunol 22:463–482PubMedGoogle Scholar
  43. 43.
    Gendzekhadze K, Norman PJ, Abi-Rached L et al (2009) Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal essential diversity of KIR and HLA class I ligands. Proc Natl Acad Sci USA 106:18692–18697PubMedCentralPubMedGoogle Scholar
  44. 44.
    Parham P (2008) The genetic and evolutionary balances in human NK cell receptor diversity. Semin Immunol 20:311–316PubMedCentralPubMedGoogle Scholar
  45. 45.
    Jiang W, Johnson C, Jayaraman J et al (2012) Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors. Genome Res 22:1845–1854PubMedCentralPubMedGoogle Scholar
  46. 46.
    Pyo CW, Guethlein LA, Vu Q et al (2010) Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus. PLoS One 5:e15115PubMedCentralPubMedGoogle Scholar
  47. 47.
    Martin MP, Bashirova A, Traherne J et al (2003) Cutting edge: expansion of the KIR locus by unequal crossing over. J Immunol 171:2192–2195PubMedGoogle Scholar
  48. 48.
    Uhrberg M (2005) The KIR gene family: life in the fast lane of evolution. Eur J Immunol 35:10–15PubMedGoogle Scholar
  49. 49.
    Norman PJ, Abi-Rached L, Gendzekhadze K et al (2009) Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes. Genome Res 19:757–769PubMedCentralPubMedGoogle Scholar
  50. 50.
    Traherne JA, Martin M, Ward R et al (2010) Mechanisms of copy number variation and hybrid gene formation in the KIR immune gene complex. Hum Mol Genet 19:737–751PubMedCentralPubMedGoogle Scholar
  51. 51.
    Husain Z, Alper CA, Yunis EJ et al (2002) Complex expression of natural killer receptor genes in single natural killer cells. Immunology 106:373–380PubMedCentralPubMedGoogle Scholar
  52. 52.
    Leung W, Iyengar R, Triplett B et al (2005) Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors. J Immunol 174:6540–6545PubMedGoogle Scholar
  53. 53.
    Denis L, Gagne K, Gueglio B et al (2005) NK-KIR transcript kinetics correlate with acute graft-versus-host disease occurrence after allogeneic bone marrow transplantation. Hum Immunol 66:447–459PubMedGoogle Scholar
  54. 54.
    Alves LG, Rajalingam R, Canavez F (2009) A novel real-time PCR method for KIR genotyping. Tissue Antigens 73:188–191PubMedGoogle Scholar
  55. 55.
    Koehler RN, Walsh AM, Moqueet N et al (2009) High-throughput genotyping of KIR2DL2/L3, KIR3DL1/S1, and their HLA class I ligands using real-time PCR. Tissue Antigens 74:73–80PubMedGoogle Scholar
  56. 56.
    Hong HA, Loubser AS, de Assis Rosa D et al (2011) Killer-cell immunoglobulin-like receptor genotyping and HLA killer-cell immunoglobulin-like receptor-ligand identification by real-time polymerase chain reaction. Tissue Antigens 78:185–194PubMedCentralPubMedGoogle Scholar
  57. 57.
    Houtchens KA, Nichols RJ, Ladner MB et al (2007) High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles. Immunogenetics 59:525–537PubMedCentralPubMedGoogle Scholar
  58. 58.
    Chainonthee W, Böttcher G, Gagne K et al (2010) Improved KIR gene and HLA-C KIR ligand sequence-specific primer polymerase chain reaction genotyping using whole genome amplification. Tissue Antigens 76:135–143PubMedGoogle Scholar
  59. 59.
    Khan F, Liacini A, Arora E et al (2012) Assessment of fidelity and utility of the whole-genome amplification for the clinical tests offered in a histocompatibility and immunogenetics laboratory. Tissue Antigens 79:372–379PubMedGoogle Scholar
  60. 60.
    Ndlovu BG, Danaviah S, Moodley E et al (2012) Use of dried blood spots for the determination of genetic variation of interleukin-10, killer immunoglobulin-like receptor and HLA class I genes. Tissue Antigens 79:114–122PubMedCentralPubMedGoogle Scholar
  61. 61.
    Ordóñez D, Moraru M, Gómez-Lozano N et al (2012) KIR typing by non-sequencing methods: polymerase-chain reaction with sequence-specific primers. Methods Mol Biol 882:415–430PubMedGoogle Scholar
  62. 62.
    Petersdorf EW, Malkki M, Hsu K et al (2013) 16th IHIW: international histocompatibility working group in hematopoietic cell transplantation. Int J Immunogenet 40:2–10PubMedGoogle Scholar
  63. 63.
    Ashouri E, Ghaderi A, Reed EF et al (2009) A novel duplex SSP-PCR typing method for KIR gene profiling. Tissue Antigens 74:62–67PubMedGoogle Scholar
  64. 64.
    Sun JY, Gaidulis L, Miller MM et al (2004) Development of a multiplex PCR-SSP method for Killer-cell immunoglobulin-like receptor genotyping. Tissue Antigens 64:462–468PubMedGoogle Scholar
  65. 65.
    Tajik N, Shahsavar F, Nasiri M et al (2010) Compound KIR-HLA genotype analyses in the Iranian population by a novel PCR-SSP assay. Int J Immunogenet 37:159–168PubMedGoogle Scholar
  66. 66.
    Kulkarni S, Martin MP, Carrington M (2010) KIR genotyping by multiplex PCR-SSP. Methods Mol Biol 612:365–375PubMedCentralPubMedGoogle Scholar
  67. 67.
    Abalos AT, Eggers R, Hogan M et al (2011) Design and validation of a multiplex specific primer-directed polymerase chain reaction assay for killer-cell immunoglobulin-like receptor genetic profiling. Tissue Antigens 77:143–148PubMedGoogle Scholar
  68. 68.
    Crum KA, Logue SE, Curran MD et al (2000) Development of a PCR-SSOP approach capable of defining the natural killer cell inhibitory receptor (KIR) gene sequence repertoires. Tissue Antigens 56:313–326PubMedGoogle Scholar
  69. 69.
    Cook MA, Norman PJ, Curran MD et al (2003) A multi-laboratory characterization of the KIR genotypes of 10th International Histocompatibility Workshop cell lines. Hum Immunol 64:567–571PubMedGoogle Scholar
  70. 70.
    Nong T, Saito K, Blair L et al (2007) KIR genotyping by reverse sequence-specific oligonucleotide methodology. Tissue Antigens 69:92–95PubMedGoogle Scholar
  71. 71.
    Park HJ, Oh Y, Kang HJ et al (2011) A gene-specific primer extension and liquid bead array system for killer-cell immunoglobulin-like receptor genotyping. Tissue Antigens 77:251–256PubMedGoogle Scholar
  72. 72.
    Hsu KC, Liu XR, Selvakumar A et al (2002) Killer Ig-like receptor haplotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J Immunol 169:5118–5129PubMedGoogle Scholar
  73. 73.
    Gourraud PA, Gagne K, Bignon JD et al (2007) Preliminary analysis of a KIR haplotype estimation algorithm: a simulation study. Tissue Antigens 69(Suppl 1):96–100PubMedGoogle Scholar
  74. 74.
    Hollenbach JA, Meenagh A, Sleator C et al (2010) Report from the killer immunoglobulin-like receptor (KIR) anthropology component of the 15th International Histocompatibility Workshop: worldwide variation in the KIR loci and further evidence for the co-evolution of KIR and HLA. Tissue Antigens 76:9–17PubMedGoogle Scholar
  75. 75.
    Sanchez-Mazas A, Fernandez-Viña M, Middleton D et al (2011) Immunogenetics as a tool in anthropological studies. Immunology 133:143–164PubMedCentralPubMedGoogle Scholar
  76. 76.
    Gendzekhadze K, Norman PJ, Abi-Rached L et al (2006) High KIR diversity in Amerindians is maintained using few gene-content haplotypes. Immunogenetics 58:474–480PubMedGoogle Scholar
  77. 77.
    Mullighan CG, Petersdorf EW (2006) Genomic polymorphism and allogeneic hematopoietic transplantation outcome. Biol Blood Marrow Transplant 12:19–27PubMedGoogle Scholar
  78. 78.
    Beksaç M, Dalva K (2012) Role of killer immunoglobulin-like receptor and ligand matching in donor selection. Bone Marrow Res 2012: article ID 271695, 6 pagesGoogle Scholar
  79. 79.
    Villard J (2011) The role of natural killer cells in human solid organ and tissue transplantation. J Innate Immun 3:395–402PubMedGoogle Scholar
  80. 80.
    Martin MP, Carrington M (2008) KIR locus polymorphisms: genotyping and disease association analysis. Methods Mol Biol 415:49–64PubMedGoogle Scholar
  81. 81.
    Shilling HG, Guethlein LA, Cheng NW et al (2002) Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype. J Immunol 168:2307–2315PubMedGoogle Scholar
  82. 82.
    Norman PJ, Abi-Rached L, Gendzekhadze K et al (2007) Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nat Genet 39:1092–1099PubMedGoogle Scholar
  83. 83.
    Sun JY, Oki A, Senitzer D (2008) Alleles and intron polymorphism of KIR3DL1 shown by combination of allele group-specific primers and sequencing. Tissue Antigens 72:578–580PubMedGoogle Scholar
  84. 84.
    Gardiner CM, Guethlein LA, Shilling HG et al (2001) Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. J Immunol 166:2992–3001PubMedGoogle Scholar
  85. 85.
    Vierra-Green C, Roe D, Hou L et al (2012) Allele-level haplotype frequencies and pairwise linkage disequilibrium for 14 KIR loci in 506 European-American individuals. PLoS One 7:e47491PubMedCentralPubMedGoogle Scholar
  86. 86.
    Halfpenny IA, Middleton D, Barnett YA et al (2004) Investigation of killer cell immunoglobulin-like receptor gene diversity: IV. KIR3DL1/S1. Hum Immunol 65:602–612PubMedGoogle Scholar
  87. 87.
    Maxwell LD, Williams F, Gilmore P et al (2004) Investigation of killer cell immunoglobulin-like receptor gene diversity: II. KIR2DS4. Hum Immunol 65:613–621PubMedGoogle Scholar
  88. 88.
    Williams F, Meenagh A, Sleator C et al (2004) Investigation of killer cell immunoglobulin-like receptor gene diversity: I. KIR2DL4. Hum Immunol 65:31–38PubMedGoogle Scholar
  89. 89.
    Gonzalez A, Meenagh A, Sleator C et al (2008) Investigation of killer cell immunoglobulin-like receptor (KIR) gene diversity: KIR2DL2, KIR2DL5 and KIR2DS5. Tissue Antigens 72:11–20PubMedGoogle Scholar
  90. 90.
    Bari R, Leung M, Turner VE et al (2011) Molecular determinant-based typing of KIR alleles and KIR ligands. Clin Immunol 138:274–281PubMedGoogle Scholar
  91. 91.
    Gonzalez A, McErlean C, Meenagh A et al (2009) Killer cell immunoglobulin-like receptor allele discrimination by high-resolution melting. Hum Immunol 70:858–863PubMedGoogle Scholar
  92. 92.
    Thananchai H, Gillespie G, Martin MP et al (2007) Cutting edge: allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol 178:33–37PubMedGoogle Scholar
  93. 93.
    Roberts CH, Turino C, Madrigal JA et al (2007) Enrichment of individual KIR2DL4 sequences from genomic DNA using long-template PCR and allele-specific hybridization to magnetic bead-bound oligonucleotide probes. Tissue Antigens 69:597–601PubMedGoogle Scholar
  94. 94.
    Roberts CH, Madrigal JA, Marsh SG (2007) Cloning and sequencing alleles of the KIR2DL4 gene from genomic DNA samples. Tissue Antigens 69:88–91PubMedGoogle Scholar
  95. 95.
    Du Z, Sharma SK, Spellman S et al (2008) KIR2DL5 alleles mark certain combination of activating KIR genes. Genes Immun 9:470–480PubMedGoogle Scholar
  96. 96.
    Schellekens J, Tilanus MG, Rozemuller EH (2008) The elucidation of KIR2DL4 gene polymorphism. Mol Immunol 45:1900–1906PubMedGoogle Scholar
  97. 97.
    Hou L, Chen M, Steiner N et al (2012) Killer cell immunoglobulin-like receptors (KIR) typing by DNA sequencing. Methods Mol Biol 882:431–468PubMedCentralPubMedGoogle Scholar
  98. 98.
    Witt CS, Martin A, Christiansen FT (2000) Detection of KIR2DL4 alleles by sequencing and SSCP reveals a common allele with a shortened cytoplasmic tail. Tissue Antigens 56:248–257PubMedGoogle Scholar
  99. 99.
    Yawata M, Yawata N, Draghi M et al (2006) Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. J Exp Med 203:633–645PubMedCentralPubMedGoogle Scholar
  100. 100.
    Robinson J, Mistry K, McWilliam H et al (2010) IPD—the Immuno Polymorphism Database. Nucleic Acids Res 38:D863–D869PubMedCentralPubMedGoogle Scholar
  101. 101.
    Carr WH, Pando MJ, Parham P (2005) KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand. J Immunol 175:5222–5229PubMedGoogle Scholar
  102. 102.
    O’Connor GM, Guinan KJ, Cunningham RT et al (2007) Functional polymorphism of the KIR3DL1/S1 receptor on human NK cells. J Immunol 178:235–241PubMedGoogle Scholar
  103. 103.
    Kikuchi-Maki A, Yusa S, Catina TL et al (2003) KIR2DL4 is an IL-2-regulated NK cell receptor that exhibits limited expression in humans but triggers strong IFN-gamma production. J Immunol 171:3415–3425PubMedGoogle Scholar
  104. 104.
    Martin MP, Pascal V, Yeager M et al (2007) A mutation in KIR3DS1 that results in truncation and lack of cell surface expression. Immunogenetics 59:823–881PubMedGoogle Scholar
  105. 105.
    Moretta A, Tambussi G, Bottino C et al (1990) A novel surface antigen expressed by a subset of human CD3–CD16+ natural killer cells. Role in cell activation and regulation of cytolytic function. J Exp Med 171:695–714PubMedGoogle Scholar
  106. 106.
    Shilling HG, Young N, Guethlein LA et al (2002) Genetic control of human NK cell repertoire. J Immunol 169:239–247PubMedGoogle Scholar
  107. 107.
    Rajagopalan S, Long EO (1999) A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med 189:1093–1100PubMedCentralPubMedGoogle Scholar
  108. 108.
    Goodridge JP, Witt CS, Christiansen FT et al (2003) KIR2DL4 (CD158d) genotype influences expression and function in NK cells. J Immunol 171:1768–1774PubMedGoogle Scholar
  109. 109.
    Torkar M, Norgate Z, Colonna M et al (1998) Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor complex. Eur J Immunol 28:3959–3967PubMedGoogle Scholar
  110. 110.
    Long EO, Barber DF, Burshtyn DN et al (2001) Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158). Immunol Rev 181:223–233PubMedGoogle Scholar
  111. 111.
    Andersson S, Fauriat C, Malmberg JA et al (2009) KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression. Blood 114:95–104PubMedGoogle Scholar
  112. 112.
    Santourlidis S, Trompeter HI, Weinhold S et al (2002) Crucial role of DNA methylation in determination of clonally distributed killer cell Ig-like receptor expression patterns in NK cells. J Immunol 169:4253–4261PubMedGoogle Scholar
  113. 113.
    Chan HW, Kurago ZB, Stewart CA et al (2003) DNA methylation maintains allele-specific KIR gene expression in human natural killer cells. J Exp Med 197:245–255PubMedCentralPubMedGoogle Scholar
  114. 114.
    Trompeter HI, Gomez-Lozano N, Santourlidis S et al (2005) Three structurally and functionally divergent kinds of promoters regulate expression of clonally distributed killer cell Ig-like receptors (KIR), of KIR2DL4, and of KIR3DL3. J Immunol 174:4135–4143PubMedGoogle Scholar
  115. 115.
    Colonna M, Borsellino G, Falco M et al (1993) HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells. Proc Natl Acad Sci USA 90:12000–12004PubMedCentralPubMedGoogle Scholar
  116. 116.
    Moretta A, Vitale M, Bottino C et al (1993) P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J Exp Med 178:597–604PubMedGoogle Scholar
  117. 117.
    Robinson J, Halliwell JA, McWilliam H et al (2013) The IMGT/HLA database. Nucleic Acids Res 41:D1222–D1227PubMedCentralPubMedGoogle Scholar
  118. 118.
    Wagtmann N, Rajagopalan S, Winter CC et al (1995) Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. Immunity 3:801–809PubMedGoogle Scholar
  119. 119.
    Moesta AK, Norman PJ, Yawata M et al (2008) Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol 180:3969–3979PubMedGoogle Scholar
  120. 120.
    Winter CC, Long EO (1997) A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes. J Immunol 158:4026–4028PubMedGoogle Scholar
  121. 121.
    Cella M, Longo A, Ferrara GB et al (1994) NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80. J Exp Med 180:1235–1242PubMedGoogle Scholar
  122. 122.
    Dohring C, Scheidegger D, Samaridis J et al (1996) A human killer inhibitory receptor specific for HLA-A1,2. J Immunol 156:3098–3101PubMedGoogle Scholar
  123. 123.
    Hansasuta P, Dong T, Thananchai H et al (2004) Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific. Eur J Immunol 34:1673–1679PubMedGoogle Scholar
  124. 124.
    Moffett-King A (2002) Natural killer cells and pregnancy. Nat Rev Immunol 2:656–663PubMedGoogle Scholar
  125. 125.
    Biassoni R, Pessino A, Malaspina A et al (1997) Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules. Eur J Immunol 27:3095–3099PubMedGoogle Scholar
  126. 126.
    Stewart CA, Laugier-Anfossi F, Vely F et al (2005) Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA 102:13224–13229PubMedCentralPubMedGoogle Scholar
  127. 127.
    Graef T, Moesta AK, Norman PJ et al (2009) KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C. J Exp Med 206:2557–2572PubMedCentralPubMedGoogle Scholar
  128. 128.
    Raulet DH, Vance RE (2006) Self-tolerance of natural killer cells. Nat Rev Immunol 6:520–531PubMedGoogle Scholar
  129. 129.
    Anfossi N, Andre P, Guia S et al (2006) Human NK cell education by inhibitory receptors for MHC class I. Immunity 25:331–342PubMedGoogle Scholar
  130. 130.
    Kim S, Sunwoo JB, Yang L et al (2008) HLA alleles determine differences in human natural killer cell responsiveness and potency. Proc Natl Acad Sci USA 105:3053–3058PubMedCentralPubMedGoogle Scholar
  131. 131.
    Braud VM, Allan DS, O’Callaghan CA et al (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391:795–799PubMedGoogle Scholar
  132. 132.
    Fauriat C, Andersson S, Bjorklund AT et al (2008) Estimation of the size of the alloreactive NK cell repertoire: studies in individuals homozygous for the group A KIR haplotype. J Immunol 181:6010–6019PubMedGoogle Scholar
  133. 133.
    Imai K, Matsuyama S, Miyake S et al (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356:1795–1799PubMedGoogle Scholar
  134. 134.
    D’Andrea A, Chang C, Franz-Bacon K et al (1995) Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes. J Immunol 155:2306–2310PubMedGoogle Scholar
  135. 135.
    Colonna M, Samaridis J (1995) Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science 268:405–408PubMedGoogle Scholar
  136. 136.
    Wagtmann N, Biassoni R, Cantoni C et al (1995) Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity 2:439–449PubMedGoogle Scholar
  137. 137.
    Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100PubMedGoogle Scholar
  138. 138.
    Leung W (2011) Use of NK cell activity in cure by transplant. Br J Haematol 155:14–29PubMedGoogle Scholar
  139. 139.
    Pegram HJ, Ritchie DS, Smyth MJ et al (2011) Alloreactive natural killer cells in hematopoietic stem cell transplantation. Leuk Res 35:14–21PubMedGoogle Scholar
  140. 140.
    Davies SM, Ruggieri L, DeFor T et al (2002) Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor. Blood 100:3825–3827PubMedGoogle Scholar
  141. 141.
    Lowe EJ, Turner V, Handgretinger R et al (2003) T-cell alloreactivity dominates natural killer cell alloreactivity in minimally T-cell-depleted HLA-non-identical paediatric bone marrow transplantation. Br J Haematol 123:323–326PubMedGoogle Scholar
  142. 142.
    Bishara A, De Santis D, Witt CC et al (2004) The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD. Tissue Antigens 63:204–211PubMedGoogle Scholar
  143. 143.
    Nguyen S, Kuentz M, Vernant JP et al (2008) Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation. Leukemia 22:344–352PubMedGoogle Scholar
  144. 144.
    Cooley S, Weisdorf DJ, Guethlein LA et al (2010) Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood 116:2411–2419PubMedCentralPubMedGoogle Scholar
  145. 145.
    Cooley S, Trachtenberg E, Bergemann TL et al (2009) Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood 113:726–732PubMedCentralPubMedGoogle Scholar
  146. 146.
    Hsu KC, Keever-Taylor CA, Wilton A et al (2005) Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood 105:4878–4884PubMedCentralPubMedGoogle Scholar
  147. 147.
    Willemze R, Rodrigues CA, Labopin M et al (2009) KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia 23:492–500PubMedGoogle Scholar
  148. 148.
    Hsu KC, Gooley T, Malkki M et al (2006) KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy. Biol Blood Marrow Transplant 12:828–836PubMedGoogle Scholar
  149. 149.
    Leung W, Iyengar R, Turner V et al (2004) Determinants of antileukemia effects of allogeneic NK cells. J Immunol 172:644–650PubMedGoogle Scholar
  150. 150.
    Gagne K, Brizard G, Gueglio B et al (2002) Relevance of KIR gene polymorphisms in bone marrow transplantation outcome. Hum Immunol 63:271–280PubMedGoogle Scholar
  151. 151.
    Venstrom JM, Pittari G, Gooley TA et al (2012) HLA-C-dependent prevention of leukemia relapse by donor activating KIR2DS1. N Engl J Med 367:805–816PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2014

Authors and Affiliations

  • Jennifer Schellekens
    • 1
  • Katia Gagne
    • 2
  • Steven G. E. Marsh
    • 3
  1. 1.Anthony Nolan Research Institute and UCL Cancer InstituteLondonUK
  2. 2.Etablissement Français du Sang and Université de Nantes, Immunovirologie et Polymorphisme Génétique NantesFrance
  3. 3.Laboratoire HLA-EFSNantesFrance

Personalised recommendations