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Chapter 140 : Human Natural Killer Cell Receptors

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Abstract:

Regulation of natural killer (NK) cytolytic activity is a function of engagement of one or more NK surface receptors that may be activating or inhibitory. Two of the primary sets of receptors present on human NK cells are called the killer immunoglobulin (Ig)-like receptors (KIR; previously known as the killer inhibitory receptors) and the CD94/NKG2 lectin-like receptors. These two receptor gene families and their roles in the immune response are the topic of this chapter. KIR are found primarily on NK cells but also on NKT cells (a subset of memory T cells with NK receptors), where they may modulate the adaptive immune response by competition with the T-cell receptor for ligand or by modulation of the response depending on which KIR genes are present. Because killing by NK cells is dependent on the strength of signal resulting from the inhibitory-activating receptor competition, pathogenesis can result when either the levels of the signals or the ligands are perturbed. Signaling in NK cells occurs through a variety of receptors, the most well known of which is CD16 (Fc gamma RIII). The signaling pathways are dependent upon the family of NK receptor and upon whether the receptor is activating or inhibitory. The involvement of KIR genes in viral infections and potentially in bone marrow transplantation suggests that KIR typing may have wider application in the future. For this reason, KIR typing by molecular methods is becoming standardized through an ongoing external quality control program.

Citation: Tyan D, Carrington M. 2006. Human Natural Killer Cell Receptors, p 1260-1268. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch140

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Figures

Image of FIGURE 1
FIGURE 1

HLA class I and KIR gene loci: functionally related gene clusters that exhibit extreme polymorphism. The HLA class I genes map within the MHC at 6p21.3, and the KIR genes map within the leukocyte receptor complex (LRC) at 19q13.4. The KIR gene order is shown for the two distinct KIR haplotypes that have been sequenced in their entirety. Chr., chromosome; ILT, Ig-like transcript; LAIR, leukocyte-associated Ig-like receptor; FCaR, FCα receptor; GPVI, glycoprotein VI.

Citation: Tyan D, Carrington M. 2006. Human Natural Killer Cell Receptors, p 1260-1268. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch140
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Image of FIGURE 2
FIGURE 2

The basis of KIR nomenclature: domain structure of the KIR molecules. KIR genes express molecules with either two or three extracellular Ig-like domains. The cytoplasmic domains of the inhibitory receptors are long and contain ITIM (I/VXYXXL/V) sequences, whereas a charged amino acid residue, which facilitates interaction with the adaptor molecule DAP12/KARAP, is located in the TM of the short-tailed activating receptors. KIR2DL4 contains signature sequences of both activating and inhibitory receptors. (This figure was adapted from http://web.ncbi.nlm.nih.gov:2441/books/bookres.fcgi/mo no_003/ch140d1.pdf.)

Citation: Tyan D, Carrington M. 2006. Human Natural Killer Cell Receptors, p 1260-1268. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch140
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Image of FIGURE 3
FIGURE 3

Exon-intron structure of the KIR genes. Exons 1 and 2 correspond to the leader (signal) sequence; exons 3 to 5 correspond to the Ig domains D0, D1, and D2, respectively; exons 6 and 7 correspond to the linker and TM regions, respectively; and exons 8 and 9 correspond to the cytoplasmic domain. All exons are design coded. The genes for type 1 two-domain KIR genes, KIR2DL1, KIR2DL2 and -3, and all 2DS genes, have a genomic organization identical to that of the genes encoding KIR molecules with three Ig domains, but exon 3 (encoding D0) of the genes for two-domain KIR is a pseudoexon (ψ). Exon 3 is also a pseudoexon in the KIR2DP1 gene, which also contains a pseudoexon 4. The genes encoding type 2 two-domain KIR, which include KIR2DL4, KIR2DL5A, and KIR2DL5B, are characterized by the absence of exon 4. (This figure was adapted from http://web.ncbi.nlm.nih. gov:2441/books/bookres.fcgi/mo no_003/ch140d1.pdf.)

Citation: Tyan D, Carrington M. 2006. Human Natural Killer Cell Receptors, p 1260-1268. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch140
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Image of FIGURE 4
FIGURE 4

KIR haplotypes identified by segregation analysis. Segregation analysis was used to determine the haplotypes shown, many of which are not yet definitive, since it is not always possible to determine gene copy number precisely, even when using family material ( ). KIR2DS4 alleles with the 21-bp deletion are indicated by Δ and those that were not subtyped are marked NS. (This figure was adapted from http://web.ncbi.nlm.nih.gov:2441/books/bookres.fcgi/mono_003/ch140d1.pdf.)

Citation: Tyan D, Carrington M. 2006. Human Natural Killer Cell Receptors, p 1260-1268. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch140
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References

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1. Ahmad, A., and , R. Ahmad. 2003. HIV’s evasion of host’s NK cell response and novel ways of its countering and boosting anti-HIV immunity. Curr. HIV Res. 1:295307.
2. Andre, P.,, R. Castriconi,, M. Espeli,, N. Anfossi,, T. Juarez,, S. Hue,, H. Conway,, F. Romagne,, A. Dondero,, M. Nanni,, S. Caillat-Zucman,, D. H. Raulet,, C. Bottino,, E. Vivier,, A. Moretta, and , P. Paul. 2004. Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors. Eur. J. Immunol. 34:961971.
3. Baur, M. P., and , J. A. Danilovs. 1980. Population analysis of HLA-A, B, C, DR, and other genetic markers, p. 958. In P. I. Terasaki (ed.), Histocompatibility Testing 1980. UCLA Tissue Typing Laboratory, Los Angeles, Calif.
4. Biassoni, R.,, C. Cantoni,, D. Pende,, S. Sivori,, S. Parolini,, M. Vitale,, C. Bottino, and , A. Moretta. 2001. Human natural killer cell receptors and co-receptors. Immunol. Rev. 181:203214.
5. Billadeau, D. D.,, J. L. Upshaw,, R. A. Schoon,, C. J. Dick, and , P. J. Leibson. 2003. NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. Nat. Immunol. 4:557564.
6. Braud, V. M.,, D. S. Allan,, C. A. O’Callaghan,, K. Soderstrom,, A. D’Andrea,, G. S. Ogg,, S. Lazetic,, N. T. Young,, J. I. Bell,, J. H. Phillips,, L. L. Lanier, and , A. J. McMichael. 1998. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391:795799.
7. Cantoni, C.,, S. Verdiani,, M. Falco,, A. Pessino,, M. Cilli,, R. Conte,, D. Pende,, M. Ponte,, M. S. Mikaelsson,, L. Moretta, and , R. Biassoni. 1998. p49, a putative HLA class I-specific inhibitory NK receptor belonging to the immunoglobulin superfamily. Eur. J. Immunol. 28:19801990.
8. Carrington, M., and , P. Norman. 2003. The KIR Gene Cluster. [Online.] National Library of Medicine, National Center for Biotechnology Information, Bethesda, Md. http://ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
9. Cerwenka, A., and , L. L. Lanier. 2003. NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer. Tissue Antigens 61:335343.
10. Diefenbach, A., and , D. H. Raulet. 2002. The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol. Rev. 188:921.
11. Doubrovina, E. S.,, M. M. Doubrovin,, E. Vider,, R. B. Sisson,, R. J. O’Reilly,, B. Dupont, and , Y. M. Vyas. 2003. Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J. Immunol. 171:68916899.
12. Eleme, K.,, S. B. Taner,, B. Onfelt,, L. M. Collinson,, F. E. McCann,, N. J. Chalupny,, D. Cosman,, C. Hopkins,, A. I. Magee, and , D. M. Davis. 2004. Cell surface organization of stress-inducible proteins ULBP and MICA that stimulate human NK cells and T cells via NKG2D. J. Exp. Med. 199:10051010.
13. Epling-Burnette, P. K.,, J. S. Painter,, P. Chaurasia,, F. Bai,, S. Wei,, J. Y. Djeu, and , T. P. Loughran. Jr. 2004. Dysregulated NK receptor expression in patients with lym-phoproliferative disease of granular lymphocytes. Blood 103:34313439.
14. Gomez-Lozano, N.,, C. M. Gardiner,, P. Parham, and , C. Vilches. 2002. Some human KIR haplotypes contain two KIR2DL5 genes: KIR2DL5A and KIR2DL5B. Immuno-genetics 54:314319.
15. Gonen-Gross, T.,, R. Gazit,, H. Achdout,, J. Hanna,, S. Mizrahi,, G. Markel,, V. Horejsi, and , O. Mandelboim. 2003. Special organization of the HLA-G protein on the cell surface. Hum. Immunol. 64:10111016.
16. Grau, R.,, K. S. Lang,, D. Wernet,, P. Lang,, D. Niethammer,, C. M. Pusch, and , R. Handgretinger. 2004. Cytotoxic activity of natural killer cells lacking killer-inhibitory receptors for self-HLA class I molecules against autologous hematopoietic stem cells in healthy individuals. Exp. Mol. Pathol. 76:9098.
17. Hiby, S. E.,, J. J. Walker,, K. M. O’Shaughnessy,, C. W. Redman,, M. Carrington,, J. Trowsdale, and , A. Moffett. 2004. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J. Exp. Med. 200:957965.
18. Hofmeister, V., and , E. H. Weiss. 2003. HLA-G modulates immune responses by diverse receptor interactions. Semin. Cancer Biol. 13:317323.
19. Hsu, K. C.,, X. R. Liu,, A. Selvakumar,, E. Mickelson,, R. J. O’Reilly, and , B. Dupont. 2002. Killer Ig-like receptor hap-lotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J. Immunol. 169:51185129.
20. Khakoo, S. I.,, C. L. Thio,, M. P. Martin,, C. R. Brooks,, X. Gao,, J. Astemborski,, J. Cheng,, J. J. Goedert,, D. Vlahov,, M. Hilgartner,, S. Cox,, A.-M. Little,, G. J. Alexander,, M. E. Cramp,, S. J. O’Brien,, W. M. C. Rosenberg,, D. L. Thomas, and , M. Carrington. 2004. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305:872874.
21. Kim, D. K.,, J. Kabat,, F. Borrego,, T. B. Sanni,, C. H. You, and , J. E. Coligan. 2004. Human NKG2F is expressed and can associate with DAP12. Mol. Immunol. 41:5362.
22. King, A.,, S. E. Hiby,, L. Gardner,, S. Joseph,, J. M. Bowen,, S. Verma,, T. D. Burrows, and , Y. W. Loke. 2000. Recognition of trophoblast HLA class I molecules by deci-dual NK cell receptors—a review. Placenta 21(Suppl. A): S81S85.
23. Lanier, L. L. 1998. Follow the leader: NK cell receptors for classical and nonclassical MHC class I. Cell 92:705707.
24. Lanier, L. L. 1998. NK cell receptors. Annu. Rev. Immunol. 16:359393.
25. Lanier, L. L. 2000. Turning on natural killer cells. J. Exp. Med. 191:12591262.
26. Lanier, L. L. 2003. Natural killer cell receptor signaling. Curr. Opin. Immunol. 15:308314.
27. Lanier, L. L. 2005. NK cell recognition. Annu. Rev. Immunol. 23:225274.
28. Lanier, L. L., and , J. H. Phillips. 1996. Inhibitory MHC class I receptors on NK cells and T cells. Immunol. Today 17:8691.
29. Lanier, L. L.,, B. Corliss, and , J. H. Phillips. 1997. Arousal and inhibition of human NK cells. Immunol. Rev. 155:145154.
30. Liang, S.,, H. Wei,, R. Sun, and , Z. Tian. 2003. IFNalpha regulates NK cell cytotoxicity through STAT1 pathway. Cytokine 23:190199.
31. Lopez-Botet, M.,, A. Angulo, and , A. Guma. 2004. Natural killer cell receptors for major histocompatibility complex class I and related molecules in cytomegalovirus infection. Tissue Antigens 63:195203.
32. Mandelboim, O.,, L. Pazmany,, D. M. Davis,, M. Vales-Gomez,, H. T. Reyburn,, B. Rybalov, and , J. L. Strominger. 1997. Multiple receptors for HLA-G on human natural killer cells. Proc. Natl. Acad. Sci. USA 94:1466614670.
33. Martin, A. M.,, E. M. Freitas,, C. S. Witt, and , F. T. Christiansen. 2000. The genomic organization and evolution of the natural killer immunoglobulin-like receptor (KIR) gene cluster. Immunogenetics 51:268280.
34. Martin, M. P.,, X. Gao,, J. H. Lee,, G. W. Nelson,, R. Detels., J. J. Goedert,, S. Buchbinder,, K. Hoots,, D. Vlahov,, J. Trowsdale,, M. Wilson,, S. J. O’Brien, and , M. Carrington. 2002. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat. Genet. 31:429434.
35. Natarajan, K.,, N. Dimasi,, J. Wang,, R. A. Mariuzza, and , D. H. Margulies. 2002. Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination. Annu. Rev. Immunol. 20:853885.
36. Nelson, G. W,, M. P. Martin,, D. Gladman,, J. Wade,, J. Trowsdale, and , M. Carrington. 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. 173:42734276.
37. Parham, P. 2004. NK cells lose their inhibition. Science 305:786787.
38. Parham, P., and , K. L. McQueen. 2003. Alloreactive killer cells: hindrance and help for haematopoietic transplants. Nat. Rev. Immunol. 3:108122.
39. Pazmany, L.,, O. Mandelboim,, M. Vales-Gomez,, D. M. Davis,, T. C. Becker,, H. T. Reyburn,, J. D. Seebach,, J. A. Hill, and , J. L. Strominger. 1999. Human leucocyte antigen-G and its recognition by natural killer cells. J. Reprod. Immunol. 43:127137.
40. Rajagopalan, S., and , E. O. Long. 1999. A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells. J. Exp. Med. 189:10931100.
41. Raulet, D. H. 2003. Roles of the NKG2D immunoreceptor and its ligands. Nat. Rev. Immunol. 3:781790.
42. Ravetch, J. V., and , L. L. Lanier. 2000. Immune inhibitory receptors. Science 290:8489.
43. Rolle, A.,, M. Mousavi-Jazi,, M. Eriksson,, J. Odeberg,, C. Soderberg-Naucler,, D. Cosman,, K. Karre, and , C. Cerboni. 2003. Effects of human cytomegalovirus infection on ligands for the activating NKG2D receptor of NK cells: up-regulation of UL16-binding protein (ULBP)1 and ULBP2 is counteracted by the viral UL16 protein. J. Immunol. 171:902908.
44. Ruggeri, L.,, M. Capanni,, E. Urbani,, K. Perruccio,, W. D. Shlomchik,, A. Tosti,, S. Posati,, D. Rogaia,, E. Frassoni,, F. Aversa,, M. F. Martelli, and , A. Velardi. 2002. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietics transplants. Science 295:20972100.
45. Salih, H. R.,, H. Antropius,, F. Gieseke,, S. Z. Lutz,, L. Kanz,, H. G. Rammensee, and , A. Steinle. 2003. Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 102:13891396.
46. Shilling, H. G.,, L. A. Guethlein,, N. W. Cheng,, C. M. Gardiner., R. Rodriguez,, D. Tyan, and , P. Parham. 2002. Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype. J. Immunol. 168:23072315.
47. Snyder, M. R.,, T. Nakajima,, P. J. Leibson,, C. M. Weyand, and , J. J. Goronzy. 2004. Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. J. Immunol. 173:37253731.
48. Snyder, M. R.,, C. M. Weyand, and , J. J. Goronzy. 2004. The double life of NK receptors: stimulation or co-stimulation. Trends Immunol. 25:2532.
49. Staub, E.,, A. Rosenthal, and , B. Hinzmann. 2004. Systematic identification of immunoreceptor tyrosine-based inhibitory motifs in the human proteome. Cell. Signal. 16:435456.
50. Steffens, U.,, Y. Vyas,, B. Dupont, and , A. Selvakumar. 1998. Nucleotide and amino acid sequence alignment for human killer cell inhibitory receptors (KIR), 1998. Tissue Antigens 51:398413.
51. Sutherland, C. L.,, N. J. Chalupny, and , D. Cosman. 2001. The UL16-binding proteins, a novel family of MHC class I-related ligands for NKG2D, activate natural killer cell functions. Immunol. Rev. 181:185192.
52. Uhrberg, M.,, P. Parham, and , P. Wernet. 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 54:221229.
53. Ulbrecht, M.,, V. Hofmeister,, G. Yuksekdag,, J. W. Ellwart,, H. Hengel,, F. Momburg,, S. Martinozzi,, M. Reboul,, M. Pla, and , E. H. Weiss. 2003. HCMV glycoprotein US6 mediated inhibition of TAP does not affect HLA-E dependent protection of K-562 cells from NK lysis. Hum. Immunol. 64:231237.
54. Valiante, N. M.,, K. Lienert,, H. G. Shilling,, B. J. Smits, and , P. Parham. 1997. Killer cell receptors: keeping pace with MHC class I evolution. Immunol. Rev. 155:155164.
55. Varla-Leftherioti, M.,, M. Spyropoulou-Vlachou,, D. Niokou,, T. Keramitsoglou,, A. Darlamitsou,, C. Tsekoura,, M. Papadimitropoulos,, V. Lepage,, C. Balafoutas, and , C. Stavropoulos-Giokas. 2003. Natural killer (NK) cell receptors’ repertoire in couples with recurrent spontaneous abortions. Am. J. Reprod. Immunol. 49:183191.
56. Vilches, C, and , P. Parham. 2002. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu. Rev. Immunol. 20:217251.
57. Vyas, Y. M.,, H. Maniar,, C. E. Lyddane,, M. Sadelain, and , B. Dupont. 2004. Ligand binding to inhibitory killer cell Ig-like receptors induces colocalization with Src homo-logy domain 2-containing protein tyrosine phosphatase 1 and interruption of ongoing activation signals. J. Immunol. 173:15711578.
58. Winter, C. C.,, J. E. Gumperz,, P. Parham,, E. O. Long, and , N. Wagtmann. 1998. Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J. Immunol. 161:571577.
59. Wu, J.,, N. J. Chalupny,, T. J. Manley,, S. R. Riddell,, D. Cosman, and , T. Spies. 2003. Intracellular retention of the MHC class I-related chain B ligand of NKG2D by the human cytomegalovirus UL16 glycoprotein. J. Immunol. 170:41964200.
60. Wu, J. D.,, L. M. Higgins,, A. Steinle,, D. Cosman,, K. Haugk, and , S. R. Plymate. 2004. Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J. Clin. Investig. 114:560568.

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