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Gene Review

KIR3DL1  -  killer cell immunoglobulin-like receptor,...

Homo sapiens

Synonyms: AMB11, CD158 antigen-like family member E, CD158E, CD158E1, CD158e1/2, ...
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Disease relevance of KIR3DL1

  • Introduction of KIR3DL1 molecules into HLA-A*0201-restricted gp100-specific CTL resulted in inhibition of lysis of gp100+ melanomas co-expressing HLA-A*0201 and HLA-Bw4 allotypes [1].
  • Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population [2].
  • Expression of the KIR2DL receptors in NK cells using recombinant vaccinia viruses confirmed these patterns of recognition, and identified KIR2DL3 as another KIR reacting with both groups of HLA-C allotypes [3].
  • Additionally, we have tested the possible association between KIR gene content (in combination with its HLA ligand) and type 1 diabetes mellitus (T1DM) [4].
  • A population-based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia [5].

Psychiatry related information on KIR3DL1


High impact information on KIR3DL1

  • As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans [7].
  • In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured [8].
  • The strongest synergistic effect of these loci was on progression to depletion of CD4(+) T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection [8].
  • The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes [8].
  • Most contacts in the complex are between KIR and conserved HLA-C residues, but a hydrogen bond between Lys 44 of KIR2DL2 and Asn 80 of Cw3 confers the allotype specificity [9].

Chemical compound and disease context of KIR3DL1


Biological context of KIR3DL1

  • Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions [15].
  • None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4(+) HLA-B [15].
  • The KIR3DL1 genotype correlates well with levels of DX9 binding by NK cells, but not with the frequency of DX9-binding cells [16].
  • Four KIR3DL1 alleles producing high DX9 binding phenotypes were distinguished from four alleles producing low or no binding phenotypes by substitution at one or more of four positions in the encoded protein: 182 and 283 in the extracellular Ig-like domains, 320 in the transmembrane region, and 373 in the cytoplasmic tail [16].
  • The KIR2DL4 promoter drove reporter gene expression only in NK cells, while the KIR3DL1 promoter was active in a range of cell types, suggesting that the latter requires other regulatory elements for physiological expression [17].

Anatomical context of KIR3DL1


Associations of KIR3DL1 with chemical compounds


Physical interactions of KIR3DL1

  • This novel system was used to study, by site-directed mutagenesis, the role of various amino acids in KIR binding to HLA-C ligand [25].
  • According to the "missing-self" hypothesis, KIR deliver inhibitory signals that prevent target-cell lysis upon binding to the self MHC class I antigens [26].
  • KIR binds in a nearly orthogonal orientation across the alpha1 and alpha2 helices of Cw3 and directly contacts positions 7 and 8 of the peptide [9].

Regulatory relationships of KIR3DL1

  • Functionally, the KIR3DL1 receptors expressed by five DX9-positive NK clones were not inhibiting NK-mediated cytotoxicity when tested against the 721.221 B-lymphoblastoid cell line expressing a HLA-B antigen with Bw4 epitope [27].
  • We discuss how our results for KIR2DS1 and parallel studies on KIR2DS2 relate to the association between activating KIR genes and susceptibility to autoimmune disorders [28].
  • The engagement of CD8 or activating KIR also triggered the production of TNF-alpha [29].
  • Finally, type 1 diabetic patients had an increased frequency of KIR gene haplotypes that include the activating KIR2DS3 gene, with a genetic interaction between the KIR and HLA complexes [30].
  • Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C-gamma in NK cells [31].

Other interactions of KIR3DL1

  • Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell-cell binding assay [15].
  • In NK cells, reporter gene expression driven by the KIR2DL4 promoter was greater than that driven by the KIR3DL1 promoter [17].
  • Here we demonstrate that a member of the KIR cDNA family, designated NKAT4, encodes a 70-kDa receptor specific for HLA-A3 [32].
  • In 5 (7%) of the 68 individuals in whom the KIR2DL1 gene was present and in 10 (15%) of the 67 in whom KIR3DL1 was present, the corresponding receptor was not expressed by NK cells, as determined by flow cytometry analysis [33].
  • The genes KIR3DL1, KIR2DS4 and KIR2DL3 were present on 31, 32 and 15 different B haplotypes, respectively, and 64, 65 and 40 of the total B haplotypes, respectively [34].

Analytical, diagnostic and therapeutic context of KIR3DL1


  1. 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. Bakker, A.B., Phillips, J.H., Figdor, C.G., Lanier, L.L. J. Immunol. (1998) [Pubmed]
  2. Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population. López-Vázquez, A., Miña-Blanco, A., Martínez-Borra, J., Njobvu, P.D., Suárez-Alvarez, B., Blanco-Gelaz, M.A., González, S., Rodrigo, L., López-Larrea, C. Hum. Immunol. (2005) [Pubmed]
  3. Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. Winter, C.C., Gumperz, J.E., Parham, P., Long, E.O., Wagtmann, N. J. Immunol. (1998) [Pubmed]
  4. Killer cell immunoglobulin-like receptor (KIR) genes in the Basque population: association study of KIR gene contents with type 1 diabetes mellitus. Santin, I., de Nanclares, G.P., Calvo, B., Gaafar, A., Castaño, L., Bilbao, J.R. Hum. Immunol. (2006) [Pubmed]
  5. A population-based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia. Arnheim, L., Dillner, J., Sanjeevi, C.B. Tissue Antigens (2005) [Pubmed]
  6. Chromosome 21 KIR channels in brain development. Thiery, E., Thomas, S., Vacher, S., Delezoide, A.L., Delabar, J.M., Créau, N. J. Neural Transm. Suppl. (2003) [Pubmed]
  7. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Vilches, C., Parham, P. Annu. Rev. Immunol. (2002) [Pubmed]
  8. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Martin, M.P., Gao, X., Lee, J.H., Nelson, G.W., Detels, R., Goedert, J.J., Buchbinder, S., Hoots, K., Vlahov, D., Trowsdale, J., Wilson, M., O'Brien, S.J., Carrington, M. Nat. Genet. (2002) [Pubmed]
  9. Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Boyington, J.C., Motyka, S.A., Schuck, P., Brooks, A.G., Sun, P.D. Nature (2000) [Pubmed]
  10. The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia. Cook, M.A., Milligan, D.W., Fegan, C.D., Darbyshire, P.J., Mahendra, P., Craddock, C.F., Moss, P.A., Briggs, D.C. Blood (2004) [Pubmed]
  11. Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705. Stewart-Jones, G.B., di Gleria, K., Kollnberger, S., McMichael, A.J., Jones, E.Y., Bowness, P. Eur. J. Immunol. (2005) [Pubmed]
  12. Missense mutations in the pancreatic islet beta cell inwardly rectifying K+ channel gene (KIR6.2/BIR): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians. Hani, E.H., Boutin, P., Durand, E., Inoue, H., Permutt, M.A., Velho, G., Froguel, P. Diabetologia (1998) [Pubmed]
  13. Simultaneous control of third-degree graft-versus-host disease and prevention of recurrence of juvenile myelomonocytic leukemia (JMML) with 6-mercaptopurine following fulminant JMML relapse early after KIR-mismatched bone marrow transplantation. Stachel, D.K., Leipold, A., Kuhlen, M., Gravou-Apostolatou, C., Hirv, K., Bader, P., Niemeyer, C.M., Beck, J.D., Holter, W. J. Pediatr. Hematol. Oncol. (2005) [Pubmed]
  14. Establishment and characterization of two human bladder cancer cell lines. Naito, S., Kotoh, S., Koga, H., Hasegawa, S., Yamasaki, T., Noma, H., Kumazawa, J. Hum. Cell (1996) [Pubmed]
  15. The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer. Khakoo, S.I., Geller, R., Shin, S., Jenkins, J.A., Parham, P. J. Exp. Med. (2002) [Pubmed]
  16. Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. Gardiner, C.M., Guethlein, L.A., Shilling, H.G., Pando, M., Carr, W.H., Rajalingam, R., Vilches, C., Parham, P. J. Immunol. (2001) [Pubmed]
  17. Different and divergent regulation of the KIR2DL4 and KIR3DL1 promoters. Stewart, C.A., Van Bergen, J., Trowsdale, J. J. Immunol. (2003) [Pubmed]
  18. Molecular mechanism of the activation-induced cell death inhibition mediated by a p70 inhibitory killer cell Ig-like receptor in Jurkat T cells. Chwae, Y.J., Chang, M.J., Park, S.M., Yoon, H., Park, H.J., Kim, S.J., Kim, J. J. Immunol. (2002) [Pubmed]
  19. 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. Pando, M.J., Gardiner, C.M., Gleimer, M., McQueen, K.L., Parham, P. J. Immunol. (2003) [Pubmed]
  20. Functional Polymorphism of the KIR3DL1/S1 Receptor on Human NK Cells. O'connor, G.M., Guinan, K.J., Cunningham, R.T., Middleton, D., Parham, P., Gardiner, C.M. J. Immunol. (2007) [Pubmed]
  21. Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations. Lopez-Larrea, C., Blanco-Gelaz, M.A., Torre-Alonso, J.C., Bruges Armas, J., Suarez-Alvarez, B., Pruneda, L., Couto, A.R., Gonzalez, S., Lopez-Vázquez, A., Martinez-Borra, J. Arthritis Res. Ther. (2006) [Pubmed]
  22. NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules. Litwin, V., Gumperz, J., Parham, P., Phillips, J.H., Lanier, L.L. J. Exp. Med. (1994) [Pubmed]
  23. DNA methylation maintains allele-specific KIR gene expression in human natural killer cells. Chan, H.W., Kurago, Z.B., Stewart, C.A., Wilson, M.J., Martin, M.P., Mace, B.E., Carrington, M., Trowsdale, J., Lutz, C.T. J. Exp. Med. (2003) [Pubmed]
  24. Natural killer cell acceptance of H-2 mismatch bone marrow grafts in transgenic mice expressing HLA-Cw3 specific killer cell inhibitory receptor. Cambiaggi, A., Verthuy, C., Naquet, P., Romagné, F., Ferrier, P., Biassoni, R., Moretta, A., Moretta, L., Vivier, E. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  25. Definition of polymorphic residues on killer Ig-like receptor proteins which contribute to the HLA-C binding site. Richardson, J., Reyburn, H.T., Luque, I., Valés-Gómez, M., Strominger, J.L. Eur. J. Immunol. (2000) [Pubmed]
  26. Killer cell inhibitory receptors involved in graft-versus-host disease and graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation - review. Chen, C., Huang, S.L. Zhongguo Shi Yan Xue Ye Xue Za Zhi (2004) [Pubmed]
  27. Multiple transcripts of the killer cell immunoglobulin-like receptor family, KIR3DL1 (NKB1), are expressed by natural killer cells of a single individual. Vyas, Y., Selvakumar, A., Steffens, U., Dupont, B. Tissue Antigens (1998) [Pubmed]
  28. Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Stewart, C.A., Laugier-Anfossi, F., Vély, F., Saulquin, X., Riedmuller, J., Tisserant, A., Gauthier, L., Romagné, F., Ferracci, G., Arosa, F.A., Moretta, A., Sun, P.D., Ugolini, S., Vivier, E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Regulation of gammadelta T cell survival by soluble HLA-I: involvement of CD8 and activating killer Ig-like receptors. Poggi, A., Contini, P., Catellani, S., Setti, M., Murdaca, G., Zocchi, M.R. Eur. J. Immunol. (2005) [Pubmed]
  30. Altered natural killer cells in type 1 diabetic patients. Rodacki, M., Svoren, B., Butty, V., Besse, W., Laffel, L., Benoist, C., Mathis, D. Diabetes (2007) [Pubmed]
  31. Killer cell inhibitory receptor recognition of human leukocyte antigen (HLA) class I blocks formation of a pp36/PLC-gamma signaling complex in human natural killer (NK) cells. Valiante, N.M., Phillips, J.H., Lanier, L.L., Parham, P. J. Exp. Med. (1996) [Pubmed]
  32. A human killer inhibitory receptor specific for HLA-A1,2. Döhring, C., Scheidegger, D., Samaridis, J., Cella, M., Colonna, M. J. Immunol. (1996) [Pubmed]
  33. Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors. Leung, W., Iyengar, R., Triplett, B., Turner, V., Behm, F.G., Holladay, M.S., Houston, J., Handgretinger, R. J. Immunol. (2005) [Pubmed]
  34. KIR haplotype content at the allele level in 77 Northern Irish families. Middleton, D., Meenagh, A., Gourraud, P.A. Immunogenetics (2007) [Pubmed]
  35. Low Number of Donor Activating Killer Immunoglobulin-Like Receptors (KIR) Genes but not KIR-Ligand Mismatch Prevents Relapse and Improves Disease-Free Survival in Leukemia Patients After In Vivo T-Cell Depleted Unrelated Stem Cell Transplantation. Kr??ger, N., Binder, T., Zabelina, T., Wolschke, C., Schieder, H., Renges, H., Ayuk, F., Dahlke, J., Eiermann, T., Zander, A. Transplantation (2006) [Pubmed]
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