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Polymorphisms of killer immunoglobulin-like receptors (KIRs) and HLA ligands in northeastern Thais

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Abstract

Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The functions of NK cells are partly regulated by interactions between KIRs and HLA ligands on target cells. In this study, the presence or absence of 17 KIR genes and their known HLA ligands have been investigated in 235 unrelated individuals living in northeastern Thailand (NET). Subtypes of KIR2DS4 including full length (KIR2DS4F) and deleted forms (KIR2DS4D) have also been determined. Framework genes (KIR2DL4, 3DL2, 3DL3, and 3DP1) were found in all individuals and KIR genes belonging to the A haplotype (KIR2DL1, 2DL3, 3DL1, and 2DS4) were present in more than 90 % of NET. KIR2DS4D (61.7 %) was more common than KIR2DS4F (52.8 %). A total of 33 different KIR genotypes were observed. Of these, three new genotypes were identified. The most common genotype (AA) was observed in 35.7 % of NET, and HLA-C alleles bearing the C1 epitope (HLA-C1) had the highest frequency (97 %). All individuals had at least one inhibitory KIR and its corresponding HLA ligand; 40.9 % of NET had three pairs of receptor–ligand combinations, and 18.3 % had all three receptor–ligand combinations of KIR2DL3+C1, 3DL1+Bw4, and 3DL2+A11. Surprisingly, the patterns of KIR gene frequencies in NET are more similar to those of Caucasians than Japanese, Korean, and Chinese. This is the first report on complete analysis of KIR and known HLA ligands in Thais. These data provide basic knowledge on KIR for further studies on disease associations and transplantation in northeastern Thais.

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References

  • Ashouri E, Ghaderi A, Reed EF, Rajalingam R (2009) A novel duplex SSP-PCR typing method for KIR gene profiling. Tissue Antigens 74:62–67

    Article  PubMed  CAS  Google Scholar 

  • Bakker AB, Phillips JH, Figdor CG, Lanier LL (1998) Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL. J Immunol 160:5239–5245

    PubMed  CAS  Google Scholar 

  • Caligiuri MA (2008) Human natural killer cells. Blood 112:461–469

    Article  PubMed  CAS  Google Scholar 

  • Du Z, Gjertson DW, Reed EF, Rajalingam R (2007) Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans. Immunogenetics 59:1–15

    Article  PubMed  CAS  Google Scholar 

  • Flores AC, Marcos CY, Paladino N, Capucchio M, Theiler G, Arruvito L, Pardo R, Habegger A, Williams F, Middleton D, Fainboim L (2007) KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations. Tissue Antigens 69:568–576

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Galarza FF, Christmas S, Middleton D, Jones AR (2011) Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations. Nucleic Acids Res 39:D913–D919

    Article  PubMed  CAS  Google Scholar 

  • Gourraud PA, Meenagh A, Cambon-Thomsen A, Middleton D (2010) Linkage disequilibrium organization of the human KIR superlocus: implications for KIR data analyses. Immunogenetics 62:729–740

    Article  PubMed  Google Scholar 

  • Hsu KC, Liu XR, Selvakumar A, Mickelson E, O’Reilly RJ, Dupont B (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 169:5118–5129

    PubMed  Google Scholar 

  • Jiang K, Zhu FM, Lv QF, Yan LX (2005) Distribution of killer cell immunoglobulin-like receptor genes in the Chinese Han population. Tissue Antigens 65:556–563

    Article  PubMed  CAS  Google Scholar 

  • John E, Christiansen FT, Mueller I, Schofield L, Senitzer D, Siba P, Witt CS (2012) Distinct distribution of killer-cell immunoglobulin-like receptor genes in the Mugil and Ilaita areas of Papua New Guinea. Tissue Antigens 79:263–271

    Article  PubMed  CAS  Google Scholar 

  • Karre K, Ljunggren HG, Piontek G, Kiessling R (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319:675–678

    Article  PubMed  CAS  Google Scholar 

  • Kaewmanee M, Phoksawat W, Romphruk A, Romphruk AV, Jumnainsong A, Leelayuwat C. (2013) Development of a multiplex polymerase chain reaction–sequence specific primer (PCR-SSP) method for NKG2D and NKG2F single nucleotide polymorphism (SNP) typing using isothermal multiple displacement amplification (IMDA) products. Tissue Antigens 81(6):419–27. doi:10.1111/tan.12105

    Google Scholar 

  • Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, Goedert JJ, Vlahov D, Hilgartner M, Cox S, Little AM, Alexander GJ, Cramp ME, O’Brien SJ, Rosenberg WM, Thomas DL, Carrington M (2004) HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305:872–874

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Poursine-Laurent J, Truscott SM, Lybarger L, Song YJ, Yang L, French AR, Sunwoo JB, Lemieux S, Hansen TH, Yokoyama WM (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436:709–713

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Sunwoo JB, Yang L, Choi T, Song YJ, French AR, Vlahiotis A, Piccirillo JF, Cella M, Colonna M, Mohanakumar T, Hsu KC, Dupont B, Yokoyama WM (2008) HLA alleles determine differences in human natural killer cell responsiveness and potency. Proc Natl Acad Sci U S A 105:3053–3058

    Article  PubMed  CAS  Google Scholar 

  • Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274

    Article  PubMed  CAS  Google Scholar 

  • Lee YC, Chan SH, Ren EC (2008) Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore. Immunogenetics 60:645–654

    Article  PubMed  Google Scholar 

  • Leelayuwat C, Srisuk T, Paechaiyaphum R, Limpaiboon T, Romphruk A, Romphruk AV (1997) Production and evaluation of Taq DNA polymerase. J Med Assoc Thai 80(suppl 1):S129–S137

    PubMed  Google Scholar 

  • Leelayuwat C, Romphruk AV (2003) Molecular techniques in routine medical laboratory: HLA typing by KKU SSP typing kit. J Med Tech Assoc Thailand 31:292–307

    Google Scholar 

  • Middleton D, Gonzelez F (2010) The extensive polymorphism of KIR genes. Immunology 129:8–19

    Article  PubMed  CAS  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  • Mingari MC, Ponte M, Vitale C, Bellomo R, Moretta L (2000) Expression of HLA class I-specific inhibitory receptors in human cytolytic T lymphocytes: a regulated mechanism that controls T-cell activation and function. Hum Immunol 61:44–50

    Article  PubMed  CAS  Google Scholar 

  • Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P (2008) Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol 180:3969–3979

    PubMed  CAS  Google Scholar 

  • Norman PJ, Stephens HA, Verity DH, Chandanayingyong D, Vaughan RW (2001) Distribution of natural killer cell immunoglobulin-like receptor sequences in three ethnic groups. Immunogenetics 52:195–205

    Article  PubMed  CAS  Google Scholar 

  • Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201–214

    Article  PubMed  CAS  Google Scholar 

  • Purdy AK, Campbell KS (2009) Natural killer cells and cancer: regulation by the killer cell Ig-like receptors (KIR). Cancer Biol Ther 8:2211–2220

    Article  PubMed  Google Scholar 

  • Rajalingam R, Du Z, Meenagh A, Luo L, Kavitha VJ, Pavithra-Arulvani R, Vidhyalakshmi A, Sharma SK, Balazs I, Reed EF, Pitchappan RM, Middleton D (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 60:207–217

    Article  PubMed  CAS  Google Scholar 

  • Rajalingam R, Krausa P, Shilling HG, Stein JB, Balamurugan A, McGinnis MD, Cheng NW, Mehra NK, Parham P (2002) Distinctive KIR and HLA diversity in a panel of north Indian Hindus. Immunogenetics 53:1009–1019

    Article  PubMed  CAS  Google Scholar 

  • Romphruk AV, Puapairoj C, Romphruk A, Barasrux S, Urwijitaroon Y, Leelayuwat C (1999) Distributions of HLA-DRB1/DQB1 alleles and haplotypes in the north-eastern Thai population: indicative of a distinct Thai population with Chinese admixtures in the central Thais. Eur J Immunogenet 26:129–133

    Article  PubMed  CAS  Google Scholar 

  • Romphruk AV, Romphruk A, Kongmaroeng C, Klumkrathok K, Paupairoj C, Leelayuwat C (2010) HLA class I and II alleles and haplotypes in ethnic Northeast Thais. Tissue Antigens 75:701–711

    Article  PubMed  CAS  Google Scholar 

  • Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, Urbani E, Negrin RS, Martelli MF, Velardi A (1999) Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 94:333–339

    PubMed  CAS  Google Scholar 

  • Shilling HG, Guethlein LA, Cheng NW, Gardiner CM, Rodriguez R, Tyan D, Parham P (2002) Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype. J Immunol 168:2307–2315

    PubMed  CAS  Google Scholar 

  • Single RM, Martin MP, Gao X, Meyer D, Yeager M, Kidd JR, Kidd KK, Carrington M (2007) Global diversity and evidence for coevolution of KIR and HLA. Nat Genet 39:1114–1119

    Article  PubMed  CAS  Google Scholar 

  • Single RM, Martin MP, Meyer D, Gao X, Carrington M (2008) Methods for assessing gene content diversity of KIR with examples from a global set of populations. Immunogenetics 60:711–725

    Article  PubMed  CAS  Google Scholar 

  • Tajik N, Shahsavar F, Nasiri M, Radjabzadeh MF (2010) Compound KIR-HLA genotype analyses in the Iranian population by a novel PCR-SSP assay. Int J Immunogenet 37:159–168

    Article  PubMed  CAS  Google Scholar 

  • Tammakorn C, Mongkolsuk T, Thammanichanond D, Pakakasama S, Kitpoka P (2011) Distribution of killer cell immunoglobulin-like receptor genes in Thai blood donors. J Med Assoc Thai 94:738–742

    PubMed  Google Scholar 

  • Tarazona-Santos E, Carvalho-Silva DR, Pettener D, Luiselli D, De Stefano GF, Labarga CM, Rickards O, Tyler-Smith C, Pena SD, Santos FR (2001) Genetic differentiation in South Amerindians is related to environmental and cultural diversity: evidence from the Y chromosome. Am J Hum Genet 68:1485–1496

    Article  PubMed  CAS  Google Scholar 

  • Toneva M, Lepage V, Lafay G, Dulphy N, Busson M, Lester S, Vu-Trien A, Michaylova A, Naumova E, McCluskey J, Charron D (2001) Genomic diversity of natural killer cell receptor genes in three populations. Tissue Antigens 57:358–362

    Article  PubMed  CAS  Google Scholar 

  • Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ (2001) The genomic context of natural killer receptor extended gene families. Immunol Rev 181:20–38

    Article  PubMed  CAS  Google Scholar 

  • Uhrberg M (2005) The KIR gene family: life in the fast lane of evolution. Eur J Immunol 35:10–15

    Article  PubMed  CAS  Google Scholar 

  • Uhrberg M, Parham P, Wernet P (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 54:221–229

    Article  PubMed  CAS  Google Scholar 

  • Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, Lanier LL, Parham P (1997) Human diversity in killer cell inhibitory receptor genes. Immunity 7:753–763

    Article  PubMed  CAS  Google Scholar 

  • Vilches C, Castano J, Gomez-Lozano N, Estefania E (2007) Facilitation of KIR genotyping by a PCR-SSP method that amplifies short DNA fragments. Tissue Antigens 70:415–422

    Article  PubMed  CAS  Google Scholar 

  • Wende H, Colonna M, Ziegler A, Volz A (1999) Organization of the leukocyte receptor cluster (LRC) on human chromosome 19q13.4. Mamm Genome 10:154–160

    Article  PubMed  CAS  Google Scholar 

  • Whang DH, Park H, Yoon JA, Park MH (2005) Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families. Hum Immunol 66:146–154

    Article  PubMed  CAS  Google Scholar 

  • Wu GQ, Zhao YM, Lai XY, Yang KL, Zhu FM, Zhang W, Wang W, Luo Y, Tan YM, Wang YJ, Cao WJ, Huang H (2009) Distribution of killer-cell immunoglobulin-like receptor genes in Eastern mainland Chinese Han and Taiwanese Han populations. Tissue Antigens 74:499–507

    Article  PubMed  CAS  Google Scholar 

  • Yawata M, Yawata N, McQueen KL, Cheng NW, Guethlein LA, Rajalingam R, Shilling HG, Parham P (2002) Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression. Immunogenetics 54:543–550

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Office of the Higher Education Commission, Thailand, through a Ph.D. scholarship (231/2551) to SC and CL. We also wish to acknowledge the support of the Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University and the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region Cluster (SHeP-GMS) (NRU542022), Khon Kaen University.

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Correspondence to Chanvit Leelayuwat.

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Chaisri, S., Kitcharoen, K., Romphruk, A.V. et al. Polymorphisms of killer immunoglobulin-like receptors (KIRs) and HLA ligands in northeastern Thais. Immunogenetics 65, 645–653 (2013). https://doi.org/10.1007/s00251-013-0716-7

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  • DOI: https://doi.org/10.1007/s00251-013-0716-7

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