Immunogenetics pp 391-414 | Cite as

Overview of the Killer Cell Immunoglobulin-Like Receptor System

Part of the Methods in Molecular Biology book series (MIMB, volume 882)

Abstract

Natural killer (NK) cells are more than simple killers and have been implicated in control and clearance of malignant and virally infected cells, regulation of adaptive immune responses, rejection of bone marrow transplants, and autoimmunity and the maintenance of pregnancy. Human NK cells largely use a family of germ-line encoded killer cell immunoglobulin-like receptors (KIR) to respond to the perturbations from self-HLA class I molecules present on infected, malignant, or HLA-disparate fetal or allogenic transplants. Genes encoding KIR receptors and HLA class I ligands are located on different chromosomes, and both feature extraordinary diversity in the number and type of genes. The independent segregation of KIR and HLA gene families produce diversity in the number and type of KIR-HLA gene combinations inherited in individuals, which may determine their immunity and susceptibility to diseases. This chapter provides an overview of NK cells and their unprecedented phenotypic and functional diversity within and between individuals.

Key words

NK cells Innate immunity HLA KIR Polymorphism Immune genes 

Notes

Acknowledgment

This work was supported by start-up funds from the UCLA Department of Pathology and Laboratory Medicine.

References

  1. 1.
    Caligiuri MA (2008) Human natural killer cells. Blood 112:461–469Google Scholar
  2. 2.
    Vivier E et al (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331:44–49Google Scholar
  3. 3.
    Colucci F et al (2003) What does it take to make a natural killer? Nat Rev Immunol 3:413–425Google Scholar
  4. 4.
    Lee SH et al (2007) Keeping NK cells in highly regulated antiviral warfare. Trends Immunol 28:252–259Google Scholar
  5. 5.
    Smyth MJ et al (2002) New aspects of ­natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer 2:850–861Google Scholar
  6. 6.
    Sun JC et al (2010) Immune memory redefined: characterizing the longevity of natural killer cells. Immunol Rev 236:83–94Google Scholar
  7. 7.
    Cooper MA et al (2001) Human natural killer cells: a unique innate immunoregulatory role for the CD56 (bright) subset. Blood 97:3146–3151Google Scholar
  8. 8.
    Freud AG, Caligiuri MA (2006) Human natural killer cell development. Immunol Rev 214:56–72Google Scholar
  9. 9.
    Jacobs R et al (2001) CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells. Eur J Immunol 31:3121–3127Google Scholar
  10. 10.
    Fehniger TA et al (2003) CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood 101:3052–3057Google Scholar
  11. 11.
    Cooper MA et al (2004) NK cell and DC interactions. Trends Immunol 25:47–52Google Scholar
  12. 12.
    Manaster I, Mandelboim O (2008) The unique properties of human NK cells in the uterine mucosa. Placenta 29(suppl A):S60–S66Google Scholar
  13. 13.
    Colonna M (2009) Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity. Immunity 31:15–23Google Scholar
  14. 14.
    Bryceson YT, Long EO (2008) Line of attack: NK cell specificity and integration of signals. Curr Opin Immunol 20:344–352Google Scholar
  15. 15.
    Lanier LL (2003) Natural killer cell receptor signaling. Curr Opin Immunol 15:308–314Google Scholar
  16. 16.
    McQueen KL, Parham P (2002) Variable receptors controlling activation and inhibition of NK cells. Curr Opin Immunol 14:615–621Google Scholar
  17. 17.
    Moretta L et al (2000) Human NK-cell receptors. Immunol Today 21:420–422Google Scholar
  18. 18.
    Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274Google Scholar
  19. 19.
    Lanier LL (2008) Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 9:495–502Google Scholar
  20. 20.
    Valiante NM et al (1997) Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity 7:739–751Google Scholar
  21. 21.
    Biron CA (2001) Interferons alpha and beta as immune regulators—a new look. Immunity 14:661–664Google Scholar
  22. 22.
    Ljunggren HG, Karre K (1990) In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today 11:237–244Google Scholar
  23. 23.
    Lanier LL (1998) NK cell receptors. Annu Rev Immunol 16:359–393Google Scholar
  24. 24.
    Long EO et al (2001) Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158). Immunol Rev 181:223–233Google Scholar
  25. 25.
    Moretta A et al (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223Google Scholar
  26. 26.
    Vilches C, Parham P (2002) KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 20:217–251Google Scholar
  27. 27.
    Lanier LL (2008) Evolutionary struggles between NK cells and viruses. Nat Rev Immunol 8:259–268Google Scholar
  28. 28.
    Parham P (2003) Immunogenetics of killer-cell immunoglobulin-like receptors. Tissue Antigens 62:194–200Google Scholar
  29. 29.
    Abi-Rached L et al (2010) Human-specific evolution and adaptation led to major qualitative differences in the variable receptors of human and chimpanzee natural killer cells. PLoS Genet 6:e1001192Google Scholar
  30. 30.
    Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201–214Google Scholar
  31. 31.
    Uhrberg M et al (1997) Human diversity in killer cell inhibitory receptor genes. Immunity 7:753–763Google Scholar
  32. 32.
    Khakoo SI, Carrington M (2006) KIR and disease: a model system or system of models? Immunol Rev 214:186–201Google Scholar
  33. 33.
    Bashirova AA et al (2006) The killer ­immunoglobulin-like receptor gene cluster: tuning the genome for defense. Annu Rev Genomics Hum Genet 7:277–300Google Scholar
  34. 34.
    Wilson MJ et al (2000) Plasticity in the organization and sequences of human KIR/ILT gene families. Proc Natl Acad Sci USA 97:4778–4783Google Scholar
  35. 35.
    Trowsdale J (2001) Genetic and functional relationships between MHC and NK receptor genes. Immunity 15:363–374Google Scholar
  36. 36.
    Steffens U et al (1998) Nucleotide and amino acid sequence alignment for human killer cell inhibitory receptors (KIR), 1998. Tissue Antigens 51:398–413Google Scholar
  37. 37.
    Marsh SG et al (2003) Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002. Tissue Antigens 62:79–86Google Scholar
  38. 38.
    Lanier LL (2009) DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev 227:150–160Google Scholar
  39. 39.
    Marsh SG et al (2011) Nomenclature for factors of the HLA system, 2010. Tissue Antigens 75:291–455Google Scholar
  40. 40.
    Klein J, Sato A (2000) The HLA system. Second of two parts. N Engl J Med 343:782–786Google Scholar
  41. 41.
    Klein J, Sato A (2000) The HLA system. First of two parts. N Engl J Med 343:702–709Google Scholar
  42. 42.
    Boyington JC et al (2000) Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Nature 405:537–543Google Scholar
  43. 43.
    Khakoo SI et al (2002) The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer. J Exp Med 196:911–921Google Scholar
  44. 44.
    Prugnolle F et al (2005) Pathogen-driven selection and worldwide HLA class I diversity. Curr Biol 15:1022–1027Google Scholar
  45. 45.
    Parham P, Ohta T (1996) Population biology of antigen presentation by MHC class I molecules. Science 272:67–74Google Scholar
  46. 46.
    Colonna M et al (1992) Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. Proc Natl Acad Sci USA 89:7983–7985Google Scholar
  47. 47.
    Mandelboim O et al (1996) Protection from lysis by natural killer cells of group 1 and 2 specificity is mediated by residue 80 in human histocompatibility leukocyte antigen C alleles and also occurs with empty major histocompatibility complex molecules. J Exp Med 184:913–922Google Scholar
  48. 48.
    Mandelboim O et al (1997) The binding site of NK receptors on HLA-C molecules. Immunity 6:341–350Google Scholar
  49. 49.
    Colonna 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 90:12000–12004Google Scholar
  50. 50.
    Wagtmann N 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 2:439–449Google Scholar
  51. 51.
    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 158:4026–4028Google Scholar
  52. 52.
    Moesta AK 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 180:3969–3979Google Scholar
  53. 53.
    Winter CC et al (1998) Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J Immunol 161:571–577Google Scholar
  54. 54.
    Stewart CA et al (2005) Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA 102:13224–13229Google Scholar
  55. 55.
    Graef T 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 206:2557–2572Google Scholar
  56. 56.
    Gumperz JE et al (1995) The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor. J Exp Med 181:1133–1144Google Scholar
  57. 57.
    Cella M et al (1994) NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80. J Exp Med 180:1235–1242Google Scholar
  58. 58.
    Thananchai H et al (2007) Cutting edge: allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol 178:33–37Google Scholar
  59. 59.
    Pende D et al (1996) The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer. J Exp Med 184:505–518Google Scholar
  60. 60.
    Dohring C et al (1996) A human killer inhibitory receptor specific for HLA-A1,2. J Immunol 156:3098–3101Google Scholar
  61. 61.
    Hansasuta P et al (2004) Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is ­peptide-specific. Eur J Immunol 34:1673–1679Google Scholar
  62. 62.
    Rajagopalan S, Long EO (1999) A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J Exp Med 189:1093–1100Google Scholar
  63. 63.
    Moffett-King A (2002) Natural killer cells and pregnancy. Nat Rev Immunol 2:656–663Google Scholar
  64. 64.
    Rajagopalan S et al (2006) Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol 4:e9Google Scholar
  65. 65.
    Kikuchi-Maki A 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 171:3415–3425Google Scholar
  66. 66.
    Faure M, Long EO (2002) KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. J Immunol 168:6208–6214Google Scholar
  67. 67.
    Ponte M et al (1999) Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci USA 96:5674–5679Google Scholar
  68. 68.
    Martin MP et al (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31:429–434Google Scholar
  69. 69.
    Uhrberg M et al (2002) Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes. Immunogenetics 54:221–229Google Scholar
  70. 70.
    Hsu KC 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 169:5118–5129Google Scholar
  71. 71.
    Yawata M et al (2006) Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. J Exp Med 203:633–645Google Scholar
  72. 72.
    Whang DH et al (2005) Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families. Hum Immunol 66:146–154Google Scholar
  73. 73.
    Middleton D et al (2007) KIR haplotype content at the allele level in 77 Northern Irish families. Immunogenetics 59:145–158Google Scholar
  74. 74.
    Pyo C 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:e15115Google Scholar
  75. 75.
    Yawata M et al (2002) Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family. Crit Rev Immunol 22:463–482Google Scholar
  76. 76.
    Ashouri E et al (2009) KIR gene content diversity in four Iranian populations. Immunogenetics 61:483–492Google Scholar
  77. 77.
    Shilling HG et al (2002) Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype. J Immunol 168:2307–2315Google Scholar
  78. 78.
    Norman PJ et al (2009) Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes. Genome Res 19:757–769Google Scholar
  79. 79.
    Martin AM et al (2000) The genomic organization and evolution of the natural killer immunoglobulin-like receptor (KIR) gene cluster. Immunogenetics 51:268–280Google Scholar
  80. 80.
    Williams F et al (2003) Multiple copies of KIR 3DL/S1 and KIR 2DL4 genes identified in a number of individuals. Hum Immunol 64:729–732Google Scholar
  81. 81.
    Ordonez D et al (2008) Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes. Genes Immun 9:431–437Google Scholar
  82. 82.
    Jiang K et al (2005) Distribution of killer cell immunoglobulin-like receptor genes in the Chinese Han population. Tissue Antigens 65:556–563Google Scholar
  83. 83.
    Yawata M et al (2002) Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression. Immunogenetics 54:543–550Google Scholar
  84. 84.
    Gendzekhadze K et al (2006) High KIR diversity in Amerindians is maintained using few gene-content haplotypes. Immunogenetics 58:474–480Google Scholar
  85. 85.
    Ewerton PD et al (2007) Amazonian Amerindians exhibit high variability of KIR profiles. Immunogenetics 59:625–630Google Scholar
  86. 86.
    Toneva M et al (2001) Genomic diversity of natural killer cell receptor genes in three populations. Tissue Antigens 57:358–362Google Scholar
  87. 87.
    Rajalingam R et al (2008) Distinct diversity of KIR genes in three southern Indian populations: comparison with world populations revealed a link between KIR gene content and pre-historic human migrations. Immunogenetics 60:207–217Google Scholar
  88. 88.
    Rajalingam R et al (2002) Distinctive KIR and HLA diversity in a panel of north Indian Hindus. Immunogenetics 53:1009–1019Google Scholar
  89. 89.
    Kulkarni S et al (2008) Comparison of the rapidly evolving KIR locus in Parsis and natives of India. Immunogenetics 60:121–129Google Scholar
  90. 90.
    Garcia CA et al (2003) Human KIR sequences 2003. Immunogenetics 55:227–239Google Scholar
  91. 91.
    Rajalingam R et al (2001) Identification of seventeen novel KIR variants: fourteen of them from two non-Caucasian donors. Tissue Antigens 57:22–31Google Scholar
  92. 92.
    Norman PJ et al (2007) Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nat Genet 39:1092–1099Google Scholar
  93. 93.
    Gardiner CM et al (2001) Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. J Immunol 166:2992–3001Google Scholar
  94. 94.
    Jones DC et al (2006) Nature of allelic sequence polymorphism at the KIR3DL3 locus. Immunogenetics 58:614–627Google Scholar
  95. 95.
    Hou L et al (2007) Seventeen novel alleles add to the already extensive KIR3DL3 diversity. Tissue Antigens 70:449–454Google Scholar
  96. 96.
    O’Connor GM et al (2007) Functional polymorphism of the KIR3DL1/S1 receptor on human NK cells. J Immunol 178:235–241Google Scholar
  97. 97.
    Carr WH et al (2005) KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand. J Immunol 175:5222–5229Google Scholar
  98. 98.
    Maxwell LD 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 60:254–258Google Scholar
  99. 99.
    Du Z et al (2007) Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans. Immunogenetics 59:1–15Google Scholar
  100. 100.
    Witt CS et al (2000) Detection of KIR2DL4 alleles by sequencing and SSCP reveals a common allele with a shortened cytoplasmic tail. Tissue Antigens 56:248–257Google Scholar
  101. 101.
    Goodridge JP et al (2003) KIR2DL4 (CD158d) genotype influences expression and function in NK cells. J Immunol 171:1768–1774Google Scholar
  102. 102.
    Vilches C et al (2000) Gene structure and promoter variation of expressed and nonexpressed variants of the KIR2DL5 gene. J Immunol 165:6416–6421Google Scholar
  103. 103.
    Pando MJ et al (2003) The protein made from a common allele of KIR3DL1 (3DL1*004) is poorly expressed at cell surfaces due to substitution at positions 86 in Ig domain 0 and 182 in Ig domain 1. J Immunol 171:6640–6649Google Scholar
  104. 104.
    VandenBussche CJ et al (2006) A single polymorphism disrupts the killer Ig-like receptor 2DL2/2DL3 D1 domain. J Immunol 177:5347–5357Google Scholar
  105. 105.
    Trompeter HI 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 174:4135–4143Google Scholar
  106. 106.
    Dohring C et al (1996) Alternatively spliced forms of human killer inhibitory receptors. Immunogenetics 44:227–230Google Scholar
  107. 107.
    Raulet DH et al (2001) Regulation of the natural killer cell receptor repertoire. Annu Rev Immunol 19:291–330Google Scholar
  108. 108.
    Shilling HG et al (2002) Genetic control of human NK cell repertoire. J Immunol 169:239–247Google Scholar
  109. 109.
    Santourlidis 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 169:4253–4261Google Scholar
  110. 110.
    Chan HW et al (2003) DNA methylation maintains allele-specific KIR gene expression in human natural killer cells. J Exp Med 197:245–255Google Scholar
  111. 111.
    Andersson S et al (2009) KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression. Blood 114:95–104Google Scholar
  112. 112.
    Schonberg K et al (2011) Analyses of HLA-C-specific KIR repertoires in donors with group A and B haplotypes suggest a ligand-instructed model of NK cell receptor aquisition. Blood 117:98–107Google Scholar
  113. 113.
    Anfossi N et al (2006) Human NK cell education by inhibitory receptors for MHC class I. Immunity 25:331–342Google Scholar
  114. 114.
    Kim S et al (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436:709–713Google Scholar
  115. 115.
    Cooley S et al (2007) A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self MHC is developmentally immature. Blood 110:578–586Google Scholar
  116. 116.
    Yokoyama WM, Kim S (2006) How do natural killer cells find self to achieve tolerance? Immunity 24:249–257Google Scholar
  117. 117.
    Raulet DH, Vance RE (2006) Self-tolerance of natural killer cells. Nat Rev Immunol 6:520–531Google Scholar
  118. 118.
    Bix M et al (1991) Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349:329–331Google Scholar
  119. 119.
    Furukawa H et al (1999) Tolerance of NK and LAK activity for HLA class I-deficient targets in a TAP1-deficient patient (bare lymphocyte syndrome type I). Hum Immunol 60:32–40Google Scholar
  120. 120.
    Yu J et al (2007) Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands. J Immunol 179:5977–5989Google Scholar
  121. 121.
    Chang C et al (1995) Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Immunol 25:2433–2437Google Scholar
  122. 122.
    Uhrberg M et al (2001) The repertoire of killer cell Ig-like receptor and CD94:NKG2A receptors in T cells: clones sharing identical alpha beta TCR rearrangement express highly diverse killer cell Ig-like receptor patterns. J Immunol 166:3923–3932Google Scholar
  123. 123.
    Single RM et al (2007) Global diversity and evidence for coevolution of KIR and HLA. Nat Genet 39:1114–1119Google Scholar
  124. 124.
    Gendzekhadze K 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 106:18692–18697Google Scholar
  125. 125.
    Khakoo SI et al (2004) HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305:872–874Google Scholar
  126. 126.
    Hiby SE et al (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 200:957–965Google Scholar
  127. 127.
    Hiby SE et al (2011) Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2. J Clin Invest 120:4102–4110Google Scholar
  128. 128.
    Terme M et al (2008) Natural killer cell-directed therapies: moving from unexpected results to successful strategies. Nat Immunol 9:486–494Google Scholar
  129. 129.
    Levinson RD et al (2010) Killer cell immunoglobulin-like receptor gene-cluster 3DS1-2DL5-2DS1-2DS5 predisposes susceptibility to Vogt-Koyanagi-Harada syndrome in Japanese individuals. Hum Immunol 71:192–194Google Scholar
  130. 130.
    Lopez-Vazquez A et al (2005) Protective effect of the HLA-Bw4I80 epitope and the killer cell immunoglobulin-like receptor 3DS1 gene against the development of hepatocellular carcinoma in patients with hepatitis C virus infection. J Infect Dis 192:162–165Google Scholar
  131. 131.
    Bonagura VR et al (2010) Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis. Hum Immunol 71:212–219Google Scholar
  132. 132.
    Carrington M et al (2005) Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med 201:1069–1075Google Scholar
  133. 133.
    Appelbaum FR (2003) The current status of hematopoietic cell transplantation. Annu Rev Med 54:491–512Google Scholar
  134. 134.
    Ruggeri L et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100Google Scholar
  135. 135.
    Giebel S et al (2003) Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood 102:814–819Google Scholar
  136. 136.
    Davies SM et al (2002) Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor. Blood 100:3825–3827Google Scholar
  137. 137.
    Kawase T et al (2009) HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism. Blood 113:2851–2858Google Scholar
  138. 138.
    Clausen J et al (2007) Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation. Clin Exp Immunol 148:520–528Google Scholar
  139. 139.
    Willemze R et al (2009) KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia 23:492–500Google Scholar
  140. 140.
    Pende D et al (2009) Anti-leukemia activity of alloreactive NK cells in KIR ligand-­mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood 113:3119–3129Google Scholar
  141. 141.
    Lowe EJ 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 123:23–326Google Scholar
  142. 142.
    Farag SS et al (2006) The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: a report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and the Dutch registry. Biol Blood Marrow Transplant 12:876–884Google Scholar
  143. 143.
    Cooley S et al (2010) Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood 116:2411–2419Google Scholar
  144. 144.
    Venstrom JM et al (2010) Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation. Blood 115:3162–3165Google Scholar
  145. 145.
    Sivori S et al (2011) Natural killer cells expressing the KIR2DS1-activating receptor efficiently kill T-cell blasts and dendritic cells: implications in haploidentical HSCT. Blood 117:4284–4292Google Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLAUniversity of CaliforniaLos AngelesUSA

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