Skip to main content

Advertisement

SpringerLink
Log in

KIR3DL1/S1 genotypes and KIR2DS4 allelic variants in the AB KIR genotypes are associated with Plasmodium-positive individuals in malaria infection

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The importance of innate immunity in malaria has been suggested for early protection from maturation and multiplication of Plasmodium parasites injected via infected mosquitoes. In this study, the killer cell immunoglobulin-like receptor (KIR) genes in innate immunity were investigated for an association with malaria in the comparison between Plasmodium-positive and Plasmodium-negative Melanesian individuals in the Solomon Islands, one of the most hyperendemic malaria regions in the world. The higher frequency of a pair of KIR3DL1 and KIR2DS4 was observed in the Plasmodium-positive individuals, which led to the investigation of KIR3DL1/S1 genotypes in concert with KIR2DS4 allelic variants. The positive individuals showed the highest frequency of KIR3DL1/KIR3DS1 heterozygosity, which might suggest the masking of activating KIR3DS1 by inhibitory KIR3DL1 at allelic levels to maintain the KIR3DS1-driven activation of natural killer cells diminished in controlling Plasmodium proliferation. The extended analysis with A/B genotypes further revealed the trend of parasitic positive individuals to be KIR3DL1/KIR3DS1 heterozygous in pair with KIR2DS4 nondeleted variants in a set of KIR genes inheritable as the AB genotypes. To the best of our knowledge, this study is the first KIR investigation of the malaria-infected population, which strengthened the potential associations of KIR with malaria pathogenesis. The balance of inhibitory and activating KIR3D genes (KIR3DL1/S1) and membrane-bound or secreted status of KIR2DS4 alleles in the interaction with the other KIR genes in the AB genotypes might constitute a part of KIR characteristics to determine resistance or susceptibility to Plasmodium parasitic infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Allen J, Gosden C, Jones R, White JP (1988) Pleistocene dates for the human occupation of New Ireland, northern Melanesia. Nature 331:707–709

    Article  CAS  PubMed  Google Scholar 

  • Artavanis-Tsakonas K, Riley EM (2002) Innate immune response to malaria: rapid induction of IFN-gamma from human NK cells by live Plasmodium falciparum-infected erythrocytes. J Immunol 169:2956–2963

    CAS  PubMed  Google Scholar 

  • Artavanis-Tsakonas K, Eleme K, McQueen KL, Cheng NW, Parham P, Davis DM, Riley EM (2003) Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes. J Immunol 171:5396–5405

    CAS  PubMed  Google Scholar 

  • Besson C, Roetynck S, Williams F, Orsi L, Amiel C, Lependeven C, Antoni G, Hermine O, Brice P, Ferme C, Carde P, Canioni D, Briere J, Raphael M, Nicolas JC, Clavel J, Middleton D, Vivier E, Abel L (2007) Association of killer cell immunoglobulin-like receptor genes with Hodgkin’s lymphoma in a familial study. PLoS ONE 2:e406

    Article  PubMed  CAS  Google Scholar 

  • Boonma P, Christensen PR, Suwanarusk R, Price RN, Russell B, Lek-Uthai U (2007) Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum. Malar J 6:124

    Article  PubMed  CAS  Google Scholar 

  • Boulet S, Sharafi S, Simic N, Bruneau J, Routy JP, Tsoukas CM, Bernard NF (2008) Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals. Aids 22:595–599

    Article  CAS  PubMed  Google Scholar 

  • Boyington JC, Motyka SA, Schuck P, Brooks AG, Sun PD (2000) Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Nature 405:537–543

    Article  CAS  PubMed  Google Scholar 

  • Boyton RJ, Altmann DM (2007) Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. Clin Exp Immunol 149:1–8

    CAS  PubMed  Google Scholar 

  • Brierley R (2005) Roll Back Malaria issue first global report. Lancet Infect Dis 5:332–333

    Article  PubMed  Google Scholar 

  • Chandramohan D, Jaffar S, Greenwood B (2002) Use of clinical algorithms for diagnosing malaria. Trop Med Int Health 7:45–52

    Article  PubMed  Google Scholar 

  • Cooke GS, Aucan C, Walley AJ, Segal S, Greenwood BM, Kwiatkowski DP, Hill AV (2003) Association of Fcgamma receptor IIa (CD32) polymorphism with severe malaria in West Africa. Am J Trop Med Hyg 69:565–568

    CAS  PubMed  Google Scholar 

  • Craig A, Scherf A (2001) Molecules on the surface of the Plasmodium falciparum infected erythrocyte and their role in malaria pathogenesis and immune evasion. Mol Biochem Parasitol 115:129–143

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • French N, Nakiyingi J, Lugada E, Watera C, Whitworth JA, Gilks CF (2001) Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. Aids 15:899–906

    Article  CAS  PubMed  Google Scholar 

  • Gaudieri S, DeSantis D, McKinnon E, Moore C, Nolan D, Witt CS, Mallal SA, Christiansen FT (2005) Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression. Genes Immun 6:683–690

    CAS  PubMed  Google Scholar 

  • Grimwade K, French N, Mbatha DD, Zungu DD, Dedicoat M, Gilks CF (2004) HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa. Aids 18:547–554

    Article  PubMed  Google Scholar 

  • Gutierrez-Rodriguez ME, Sandoval-Ramirez L, Diaz-Flores M, Marsh SG, Valladares-Salgado A, Madrigal JA, Mejia-Arangure JM, Garcia CA, Huerta-Zepeda A, Ibarra-Cortes B, Ortega-Camarillo C, Cruz M (2006) KIR gene in ethnic and Mestizo populations from Mexico. Hum Immunol 67:85–93

    Article  CAS  PubMed  Google Scholar 

  • Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM (1991) Common west African HLA antigens are associated with protection from severe malaria. Nature 352:595–600

    Article  CAS  PubMed  Google Scholar 

  • Hill AV, Elvin J, Willis AC, Aidoo M, Allsopp CE, Gotch FM, Gao XM, Takiguchi M, Greenwood BM, Townsend AR et al (1992) Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360:434–439

    Article  CAS  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 

  • Ishii A (1998) Malaria in the Solomon Islands. In: Ishii A, Nihei N, Sasa M (eds) Malaria research in the Solomon Islands. Inter Group Corp, Tokyo

    Google Scholar 

  • Ishii A, Nihei N, Arai M, Hirai M (2002) Malaria in the Solomon Islands. Occasional papers (form South Pacific Ocean Research Project reports, Department of Medical Zoology, Jichi Medical School)

  • Jiao YL, Ma CY, Wang LC, Cui B, Zhang J, You L, Chen ZJ, Li JF, Zhao YR (2008) Polymorphisms of KIRs gene and HLA-C alleles in patients with ankylosing spondylitis: possible association with susceptibility to the disease. J Clin Immunol 28:343–349

    Article  CAS  PubMed  Google Scholar 

  • Kayser M, Brauer S, Weiss G, Schiefenhovel W, Underhill PA, Stoneking M (2001) Independent histories of human Y chromosomes from Melanesia and Australia. Am J Hum Genet 68:173–190

    Article  CAS  PubMed  Google Scholar 

  • Khakoo SI, Carrington M (2006) KIR and disease: a model system or system of models? Immunol Rev 214:186–201

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi-Maki A, Yusa S, Catina TL, Campbell KS (2003) KIR2DL4 is an IL-2-regulated NK cell receptor that exhibits limited expression in humans but triggers strong IFN-gamma production. J Immunol 171:3415–3425

    CAS  PubMed  Google Scholar 

  • Korbel DS, Finney OC, Riley EM (2004) Natural killer cells and innate immunity to protozoan pathogens. Int J Parasitol 34:1517–1528

    Article  CAS  PubMed  Google Scholar 

  • Korbel DS, Newman KC, Almeida CR, Davis DM, Riley EM (2005) Heterogeneous human NK cell responses to Plasmodium falciparum-infected erythrocytes. J Immunol 175:7466–7473

    CAS  PubMed  Google Scholar 

  • Korenromp EL, Williams BG, de Vlas SJ, Gouws E, Gilks CF, Ghys PD, Nahlen BL (2005) Malaria attributable to the HIV-1 epidemic, sub-Saharan Africa. Emerg Infect Dis 11:1410–1419

    PubMed  Google Scholar 

  • Krishnegowda G, Hajjar AM, Zhu J, Douglass EJ, Uematsu S, Akira S, Woods AS, Gowda DC (2005) Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. J Biol Chem 280:8606–8616

    Article  CAS  PubMed  Google Scholar 

  • Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77:171–192

    Article  CAS  PubMed  Google Scholar 

  • Mangold KA, Manson RU, Koay ES, Stephens L, Regner M, Thomson RB Jr, Peterson LR, Kaul KL (2005) Real-time PCR for detection and identification of Plasmodium spp. J Clin Microbiol 43:2435–2440

    Article  CAS  PubMed  Google Scholar 

  • Martin MP, Gao X, Lee JH, Nelson GW, Detels R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, Trowsdale J, Wilson M, O’Brien SJ, Carrington M (2002a) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31:429–434

    CAS  PubMed  Google Scholar 

  • Martin MP, Nelson G, Lee JH, Pellett F, Gao X, Wade J, Wilson MJ, Trowsdale J, Gladman D, Carrington M (2002b) Cutting edge: susceptibility to psoriatic arthritis: influence of activating killer Ig-like receptor genes in the absence of specific HLA-C alleles. J Immunol 169:2818–2822

    CAS  PubMed  Google Scholar 

  • Martin MP, Qi Y, Gao X, Yamada E, Martin JN, Pereyra F, Colombo S, Brown EE, Shupert WL, Phair J, Goedert JJ, Buchbinder S, Kirk GD, Telenti A, Connors M, O’Brien SJ, Walker BD, Parham P, Deeks SG, McVicar DW, Carrington M (2007) Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 39:733–740

    Article  CAS  PubMed  Google Scholar 

  • Maxwell LD, Wallace A, Middleton D, Curran MD (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 60:254–258

    Article  CAS  PubMed  Google Scholar 

  • McGuire W, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D (1994) Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 371:508–510

    Article  CAS  PubMed  Google Scholar 

  • Mendez A, Granda H, Meenagh A, Contreras S, Zavaleta R, Mendoza MF, Izquierdo L, Sarmiento ME, Acosta A, Middleton D (2006) Study of KIR genes in tuberculosis patients. Tissue Antigens 68:386–389

    Article  CAS  PubMed  Google Scholar 

  • Middleton D, Williams F, Halfpenny IA (2005) KIR genes. Transpl Immunol 14:135–142

    Article  CAS  PubMed  Google Scholar 

  • Middleton D, Gonzalez A, Gilmore PM (2007a) Studies on the expression of the deleted KIR2DS4*003 gene product and distribution of KIR2DS4 deleted and nondeleted versions in different populations. Hum Immunol 68:128–134

    Article  CAS  PubMed  Google Scholar 

  • Middleton D, Meenagh A, Gourraud PA (2007b) KIR haplotype content at the allele level in 77 Northern Irish families. Immunogenetics 59:145–158

    Article  CAS  PubMed  Google Scholar 

  • Miller LH, Baruch DI, Marsh K, Doumbo OK (2002) The pathogenic basis of malaria. Nature 415:673–679

    Article  CAS  PubMed  Google Scholar 

  • Nelson GW, Martin MP, Gladman D, Wade J, Trowsdale J, Carrington M (2004) Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. J Immunol 173:4273–4276

    CAS  PubMed  Google Scholar 

  • Niokou D, Spyropoulou-Vlachou M, Darlamitsou A, Stavropoulos-Giokas C (2003) Distribution of killer cell immunoglobulin-like receptors in the Greek population. Hum Immunol 64:1167–1176

    Article  CAS  PubMed  Google Scholar 

  • Njama-Meya D, Clark TD, Nzarubara B, Staedke S, Kamya MR, Dorsey G (2007) Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children. Malar J 6:7

    Article  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  CAS  PubMed  Google Scholar 

  • Norman PJ, Carrington CV, Byng M, Maxwell LD, Curran MD, Stephens HA, Chandanayingyong D, Verity DH, Hameed K, Ramdath DD, Vaughan RW (2002) Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations. Genes Immun 3:86–95

    Article  CAS  PubMed  Google Scholar 

  • Norman PJ, Abi-Rached L, Gendzekhadze K, Korbel D, Gleimer M, Rowley D, Bruno D, Carrington CV, Chandanayingyong D, Chang YH, Crespi C, Saruhan-Direskeneli G, Fraser PA, Hameed K, Kamkamidze G, Koram KA, Layrisse Z, Matamoros N, Mila J, Park MH, Pitchappan RM, Ramdath DD, Shiau MY, Stephens HA, Struik S, Verity DH, Vaughan RW, Tyan D, Davis RW, Riley EM, Ronaghi M, Parham P (2007) Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nat Genet 39:1092–1099

    Article  CAS  PubMed  Google Scholar 

  • Paladino N, Flores AC, Marcos CY, Fainboim H, Theiler G, Arruvito L, Williams F, Middleton D, Fainboim L (2007) Increased frequencies of activating natural killer receptors are associated with liver injury in individuals who do not eliminate hepatitis C virus. Tissue Antigens 69(Suppl 1):109–111

    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  CAS  PubMed  Google Scholar 

  • Roland J, Soulard V, Sellier C, Drapier AM, Di Santo JP, Cazenave PA, Pied S (2006) NK cell responses to Plasmodium infection and control of intrahepatic parasite development. J Immunol 177:1229–1239

    CAS  PubMed  Google Scholar 

  • Schellekens J, Tilanus MG, Rozemuller EH (2008) The elucidation of KIR2DL4 gene polymorphism. Mol Immunol 45:1900–1906

    Article  CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Singh AP, Buscaglia CA, Wang Q, Levay A, Nussenzweig DR, Walker JR, Winzeler EA, Fujii H, Fontoura BM, Nussenzweig V (2007) Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite. Cell 131:492–504

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Sinha S, Mishra SK, Sharma S, Patibandla PK, Mallick PK, Sharma SK, Mohanty S, Pati SS, Mishra SK, Ramteke BK, Bhatt R, Joshi H, Dash AP, Ahuja RC, Awasthi S, Venkatesh V, Habib S (2008) Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population. Malar J 7:13

    Article  PubMed  CAS  Google Scholar 

  • Smith JD, Craig AG (2005) The surface of the Plasmodium falciparum-infected erythrocyte. Curr Issues Mol Biol 7:81–93

    PubMed  Google Scholar 

  • Stern M, Elsasser H, Honger G, Steiger J, Schaub S, Hess C (2008) The number of activating KIR genes inversely correlates with the rate of CMV infection/reactivation in kidney transplant recipients. Am J Transplant 8:1312–1317

    Article  CAS  PubMed  Google Scholar 

  • Stevenson MM, Riley EM (2004) Innate immunity to malaria. Nat Rev Immunol 4:169–180

    Article  CAS  PubMed  Google Scholar 

  • Stoneking M, Jorde LB, Bhatia K, Wilson AC (1990) Geographic variation in human mitochondrial DNA from Papua New Guinea. Genetics 124:717–733

    CAS  PubMed  Google Scholar 

  • Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, Rennenberg A, Krueger A, Pollok JM, Menard R, Heussler VT (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science 313:1287–1290

    Article  CAS  PubMed  Google Scholar 

  • Takehara T, Hayashi N (2005) Natural killer cells in hepatitis C virus infection: from innate immunity to adaptive immunity. Clin Gastroenterol Hepatol 3:S78–S81

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Trompeter HI, Gomez-Lozano N, Santourlidis S, Eisermann B, Wernet P, Vilches C, Uhrberg M (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 174:4135–4143

    CAS  PubMed  Google Scholar 

  • Tsintsof AS, Hertzberg MS, Prior JF, Mickleson KN, Trent RJ (1990) Alpha-globin gene markers identify genetic differences between Australian aborigines and Melanesians. Am J Hum Genet 46:138–143

    CAS  PubMed  Google Scholar 

  • Velickovic M, Velickovic Z, Dunckley H (2006) Diversity of killer cell immunoglobulin-like receptor genes in Pacific Islands populations. Immunogenetics 58:523–532

    Article  CAS  PubMed  Google Scholar 

  • Velickovic M, Velickovic Z, Panigoro R, Dunckley H (2009) Diversity of killer cell immunoglobulin-like receptor genes in Indonesian populations of Java, Kalimantan, Timor and Irian Jaya. Tissue Antigens 73:9–16

    Article  CAS  PubMed  Google Scholar 

  • WHO (2003) The world health report 2003: shaping the future. WHO, Geneva

    Google Scholar 

  • WHO (2005) Section II: malaria control by region. World malaria report 2005. World Health Organization, Geneva, pp 19–61

    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 

  • Yoshida A, Ishii A, Leafasia JL, Zhou D, Chen Y, Tang L, Lie C, Qiu D, Ohmae H, Ohta N (1998) Polymorphism of the tumor necrosis factor A gene in Melanesian and East-Asian populations. Immunogenetics 47:497–498

    Article  CAS  PubMed  Google Scholar 

  • Zhi-ming L, Yu-lian J, Zhao-lei F, Chun-xiao W, Zhen-fang D, Bing-chang Z, Yue-ran Z (2007) Polymorphisms of killer cell immunoglobulin-like receptor gene: possible association with susceptibility to or clearance of hepatitis B virus infection in Chinese Han population. Croat Med J 48:800–806

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the fund from Kobe University School of Medicine to the division of Infectious Disease Control.

I thank Professor Nobuo Ohta at Graduate School of Tokyo Medical and Dental University in Japan for his assistance in getting samples from the Solomon Islands, Dr. Raja Rajalingam at UCLA Immunogenetics Center, Dr. Mepur Ravindranath at Terasaki Foundation Laboratory, USA, and Mikki Ozawa at One Lambda, USA for their useful comments, Kiyoe Masuo and Shunta Kobayashi at VERITAS Corporation, Japan for technical support.

Author information

Authors and Affiliations

  1. Division of Infectious Disease Control, Department of Microbiology and Infectious Diseases, School of Medicine, Kobe University, Kobe, 650-0017, Japan

    Michiko Taniguchi & Masato Kawabata

Authors
  1. Michiko Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masato Kawabata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michiko Taniguchi.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taniguchi, M., Kawabata, M. KIR3DL1/S1 genotypes and KIR2DS4 allelic variants in the AB KIR genotypes are associated with Plasmodium-positive individuals in malaria infection. Immunogenetics 61, 717–730 (2009). https://doi.org/10.1007/s00251-009-0401-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-009-0401-z

Keywords

Search

Navigation