The Activating Receptors of Natural Killer Cells and Their Inter-Switching Potentials

doi:10.2174/1389450121666200910160929
摘要

全球癌症发病率正在增加，研究人员正在寻找源自免疫系统的特异性和非选择性疗法。已知NK细胞的杀伤激活受体与肿瘤和病毒感染细胞的免疫监视有关。这些受体属于两个主要类别，即免疫球蛋白样家族和C-凝集素样家族。尽管它们具有不同的信号途径，但所有的杀伤激活受体均具有相似的效应子功能，包括直接的细胞毒性和炎性细胞因子（如IFN-γ和TNF-α）的释放。为了转导超过细胞毒性激活阈值的信号，大多数这些受体需要协同作用。这篇综述分析了21种受体：13种免疫球蛋白样，5种凝集素样和3种其他受体。它批判性地探索了它们的结构独特性，在疾病中的作用，各自的转导信号途径以及它们作为癌症免疫治疗当前和潜在目标的地位。尽管大多数这些受体的天然配体是已知的，但要寻找具有高结合亲和力的特异性抗体，肽和多靶标小分子还需要做大量工作。
关键词: 免疫学，细胞毒性，免疫球蛋白，免疫疗法，凝集素，NK细胞。
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图形摘要

[1] 
Chaplin DD. Overview of the immune response. J Allergy Clin Immunol  2010; 125(2)(Suppl. 2): S3-S23.
[http://dx.doi.org/10.1016/j.jaci.2009.12.980] [PMID: 20176265] 
[2] 
Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol  2010; 125(2)(Suppl. 2): S24-32.
[http://dx.doi.org/10.1016/j.jaci.2009.07.016] [PMID: 19932920] 
[3] 
Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol  2010; 125(2)(Suppl. 2): S33-40.
[http://dx.doi.org/10.1016/j.jaci.2009.09.017] [PMID: 20061006] 
[4] 
Oli AN, Obialor WO, Ifeanyichukwu MO, et al. Immunoinformatics and Vaccine Development: An Overview Immunotargets Ther 2020.
[5] 
Clarkson BD, Héninger E, Harris MG, Lee J, Sandor M, Fabry Z. Innate-adaptive crosstalk: how dendritic cells shape immune responses in the CNS. Adv Exp Med Biol  2012; 946: 309-33.
[http://dx.doi.org/10.1007/978-1-4614-0106-3_18] [PMID: 21948376] 
[6] 
Shanker A, Thounaojam MC, Mishra MK, Dikov MM, Uzhachenko RV, Uzhachenko RV. Innate-Adaptive Immune Crosstalk. J Immunol Res  2015; 2015982465
[http://dx.doi.org/10.1155/2015/982465] [PMID: 26618182] 
[7] 
Molling JW, Langius JA, Langendijk JA, et al. Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol  2007; 25(7): 862-8.
[http://dx.doi.org/10.1200/JCO.2006.08.5787] [PMID: 17327607] 
[8] 
Lopez-Vergès S, Milush JM, Pandey S, et al. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood  2010; 116(19): 3865-74.
[http://dx.doi.org/10.1182/blood-2010-04-282301] [PMID: 20733159] 
[9] 
Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res  2003; 90: 127-56.
[http://dx.doi.org/10.1016/S0065-230X(03)90004-2] [PMID: 14710949] 
[10] 
Moretta L, Bottino C, Pende D, Vitale M, Mingari MC, Moretta A. Different checkpoints in human NK-cell activation. Trends Immunol  2004; 25(12): 670-6.
[http://dx.doi.org/10.1016/j.it.2004.09.008] [PMID: 15530838] 
[11] 
Akashi K, Traver D, Miyamoto T, Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature  2000; 404(6774): 193-7.
[http://dx.doi.org/10.1038/35004599] [PMID: 10724173] 
[12] 
Grzywacz B, Kataria N, Kataria N, et al. Natural killer-cell differentiation by myeloid progenitors. Blood  2011; 117(13): 3548-58.
[http://dx.doi.org/10.1182/blood-2010-04-281394] [PMID: 21173117] 
[13] 
Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A. Human natural killer cells: their origin, receptors and function. Eur J Immunol  2002; 32(5): 1205-11.
[http://dx.doi.org/10.1002/1521-4141(200205)32:5<1205::AID-IMMU1205>3.0.CO;2-Y] [PMID: 11981807] 
[14] 
Fathman JW, Bhattacharya D, Inlay MA, Seita J, Karsunky H, Weissman IL. Identification of the earliest natural killer cell-committed progenitor in murine bone marrow. Blood  2011; 118(20): 5439-47.
[http://dx.doi.org/10.1182/blood-2011-04-348912] [PMID: 21931117] 
[15] 
Inverardi L, Witson JC, Fuad SA, Winkler-Pickett RT, Ortaldo JR, Bach FH. CD3 negative “small agranular lymphocytes” are natural killer cells. J Immunol  1991; 146(11): 4048-52.
[PMID: 1827820] 
[16] 
Cooper MA, Fehniger TA. The biology of human natural killer- cell subsets. Trends Immunol  2001; 22(11): 633-40.
[17] 
Rook AH, Kehrl JH, Wakefield LM, et al. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol  1986; 136(10): 3916-20.
[PMID: 2871107] 
[18] 
Bellone G, Aste-Amezaga M, Trinchieri G, Rodeck U. Regulation of NK cell functions by TGF-beta 1. J Immunol  1995; 155(3): 1066-73.
[PMID: 7636180] 
[19] 
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol  2001; 19: 683-765.
[http://dx.doi.org/10.1146/annurev.immunol.19.1.683] [PMID: 11244051] 
[20] 
Shabsoug B, Khalil R, Abuharfeil N, Jordan N, Abuharfeil IJ. Enhancement of natural killer cell activity in vitro against human tumor cells by some plants from Jordan. J Immunotoxicol  2008; 5(3): 279-85.
[http://dx.doi.org/10.1080/15376510802312027] [PMID: 18830888] 
[21] 
Valiathan R, Lewis JE, Melillo AB, Leonard S, Ali KH, Asthana D. Evaluation of a flow cytometry-based assay for natural killer cell activity in clinical settings. Scand J Immunol  2012; 75(4): 455-62.
[http://dx.doi.org/10.1111/j.1365-3083.2011.02667.x] [PMID: 22150284] 
[22] 
De Sanctis JB, Blanca I, Bianco NE. Secretion of cytokines by natural killer cells primed with interleukin-2 and stimulated with different lipoproteins. Immunology  1997; 90(4): 526-33.
[http://dx.doi.org/10.1046/j.1365-2567.1997.00174.x] [PMID: 9176105] 
[23] 
Robertson MJ. Role of chemokines in the biology of natural killer cells. J Leukoc Biol  2002; 71(2): 173-83.
[PMID: 11818437] 
[24] 
Geiger TL, Abt MC, Gasteiger G, et al. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med  2014; 211(9): 1723-31.
[http://dx.doi.org/10.1084/jem.20140212] [PMID: 25113970] 
[25] 
Ishihara K, Hirano T. The Molecular Biology of Cytokines. Molecular basis of the cell specificity of cytokine action. Biochimica et Biophysica Acta (BBA) -. Molecular Cell Research  2002; 1592(3): 281-96.
[26] 
Brooks AG, Boyington JC, Sun PD. Natural killer cell recognition of HLA class I molecules. Rev Immunogenet  2000; 2(3): 433-48.
[PMID: 11256749] 
[27] 
Radaev S, Sun PD. Structure and function of natural killer cell surface receptors. Annu Rev Biophys Biomol Struct  2003; 32: 93-114.
[http://dx.doi.org/10.1146/annurev.biophys.32.110601.142347] [PMID: 12471063] 
[28] 
Hromadnikova I, Petra P, Sedlackova L. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp-70-Derived 14-mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors Mediators of Inflammation  2013; 2013: 405295.
[29] 
Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol  2013; 31(31): 227-58.
[http://dx.doi.org/10.1146/annurev-immunol-020711-075005] [PMID: 23516982] 
[30] 
Bryceson YT, March ME, Barber DF, Ljunggren HG, Long EO. Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med  2005; 202(7): 1001-12.
[http://dx.doi.org/10.1084/jem.20051143] [PMID: 16203869] 
[31] 
Ravetch JV, Kinet JP. Fc receptors. Annu Rev Immunol  1991; 9: 457-92.
[http://dx.doi.org/10.1146/annurev.iy.09.040191.002325] [PMID: 1910686] 
[32] 
van de Winkel JG, Capel PJA. Human IgG Fc Receptors. Austin: R.G. Landes Company 1996.
[33] 
Janeway C. Appendix II. CD antigens.Immunobiology.  (5th ed). New York: Garland 2001.
[34] 
Uciechowski P, Gessner JE, Schindler R, Schmidt RE. Fc gamma RIII activation is different in CD16+ cytotoxic T lymphocytes and natural killer cells. Eur J Immunol  1992; 22(6): 1635-8.
[http://dx.doi.org/10.1002/eji.1830220643] [PMID: 1376268] 
[35] 
Nagler A, Lanier LL, Phillips JH. Constitutive expression of high affinity interleukin 2 receptors on human CD16-natural killer cells in vivo. J Exp Med  1990; 171(5): 1527-33.
[http://dx.doi.org/10.1084/jem.171.5.1527] [PMID: 2139697] 
[36] 
Mandelboim O, Malik P, Davis DM, et al. Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. Proc Natl Acad Sci USA  1999; 96(10): 5640-4.
[http://dx.doi.org/10.1073/pnas.96.10.5640] [PMID: 10318937] 
[37] 
Blázquez-Moreno A, Park S, Im W, Call MJ, Call ME, Reyburn HT. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules. Proc Natl Acad Sci USA  2017; 114(28): E5645-54.
[http://dx.doi.org/10.1073/pnas.1706483114] [PMID: 28652325] 
[38] 
Barb W, Adam K, Patel R, Jacob TR, Ganesh PS. N-glycan composition impacts CD16A structure and antibody binding on natural killer cells The FASEB Journal 2017.
[39] 
Ahmed AA, Keremane SR, Vielmetter J, Bjorkman PJ. Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcγRIIIa. J Struct Biol  2016; 194(1): 78-89.
[http://dx.doi.org/10.1016/j.jsb.2016.02.001] [PMID: 26850169] 
[40] 
Wirthmueller U, Kurosaki T, Murakami MS, Ravetch JV. Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain. J Exp Med  1992; 175(5): 1381-90.
[http://dx.doi.org/10.1084/jem.175.5.1381] [PMID: 1314888] 
[41] 
Trinchieri G, Valiante N. Receptors for the Fc fragment of IgG on natural killer cells. Nat Immun  1993; 12(4-5): 218-34.
[PMID: 8257828] 
[42] 
Anegón I, Cuturi MC, Trinchieri G, Perussia B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med  1988; 167(2): 452-72.
[http://dx.doi.org/10.1084/jem.167.2.452] [PMID: 2831292] 
[43] 
Mota G, Moldovan I, Calugaru A, et al. Interaction of human immunoglobulin G with CD16 on natural killer cells: ligand clearance, FcgammaRIIIA turnover and effects of metalloproteinases on FcgammaRIIIA-mediated binding, signal transduction and killing. Scand J Immunol  2004; 59(3): 278-84.
[http://dx.doi.org/10.1111/j.0300-9475.2004.01398.x] [PMID: 15030579] 
[44] 
Li OM, Flavell RA. Cytokine Regulation of Immune Tolerance to Tumors.Cancer Immunotherapy: Immune Suppression and Tumor Growth.   2007; pp. pp. 43-61.
[http://dx.doi.org/10.1016/B978-012372551-6/50068-7] 
[45] 
Peruzzi G, Femnou L, Gil-Krzewska A, et al. Membrane-type 6 matrix metalloproteinase regulates the activation-induced downmodulation of CD16 in human primary NK cells J Immunol 2013.
[46] 
Romee R, Foley B, Lenvik T, et al. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood  2013; 121(18): 3599-608.
[http://dx.doi.org/10.1182/blood-2012-04-425397] [PMID: 23487023] 
[47] 
Vidranski V, Laskaj R, Sikiric D, Skerk V. Platelet satellitism in infectious disease? Biochem Med (Zagreb)  2015; 25(2): 285-94.
[http://dx.doi.org/10.11613/BM.2015.030] [PMID: 26110042] 
[48] 
Krzywinska E, Allende-Vega N, Cornillon A, et al. Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers. EBioMedicine  2015; 2(10): 1364-76.
[http://dx.doi.org/10.1016/j.ebiom.2015.08.021] [PMID: 26629531] 
[49] 
Jabir NR, Firoz CK, Ahmed F, et al. Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery Disease. Immunol Invest  2017; 46(5): 526-35.
[http://dx.doi.org/10.1080/08820139.2017.1306866] [PMID: 28414590] 
[50] 
Hazenbos WL, Gessner JE, Hofhuis FM, et al. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc γ RIII (CD16) deficient mice. Immunity  1996; 5(2): 181-8.
[http://dx.doi.org/10.1016/S1074-7613(00)80494-X] [PMID: 8769481] 
[51] 
Kelly JA, Griffin ME, Fava RA, et al. Inhibition of arterial lesion progression in CD16-deficient mice: evidence for altered immunity and the role of IL-10. Cardiovasc Res  2010; 85(1): 224-31.
[http://dx.doi.org/10.1093/cvr/cvp300] [PMID: 19720605] 
[52] 
Leong AC, Kumarason SY, Leong F, Joel WM. Manual of Diagnostic Cytology (2nd ed) Greenwich Medical Media, Ltd.   2003; p. 61.
[53] 
Yang JJ, Ye Y, Carroll A, Yang W, Lee HW. Structural biology of the cell adhesion protein CD2: alternatively folded states and structure-function relation. Curr Protein Pept Sci  2001; 2(1): 1-17.
[http://dx.doi.org/10.2174/1389203013381251] [PMID: 12369898] 
[54] 
Wyss DF, Choi JS, Li J, et al. Conformation and function of the N-linked glycan in the adhesion domain of human CD2. Science  1995; 269(5228): 1273-8.
[http://dx.doi.org/10.1126/science.7544493] [PMID: 7544493] 
[55] 
Recny MA, Luther MA, Knoppers MH, et al. N-glycosylation is required for human CD2 immunoadhesion functions. J Biol Chem  1992; 267(31): 22428-34.
[PMID: 1385399] 
[56] 
Withka JM, Wyss DF, Wagner G, Arulanandam AR, Reinherz EL, Recny MA. Structure of the glycosylated adhesion domain of human T lymphocyte glycoprotein CD2. Structure  1993; 1(1): 69-81.
[http://dx.doi.org/10.1016/0969-2126(93)90009-6] [PMID: 7915183] 
[57] 
Chen HA, Pfuhl M, Driscoll PC. The pH dependence of CD2 domain 1 self-association and 15N chemical exchange broadening is correlated with the anomalous pKa of Glu41. Biochemistry  2002; 41(50): 14680-8.
[http://dx.doi.org/10.1021/bi026447x] [PMID: 12475217] 
[58] 
Wilkins AL, Yang W, Yang JJ. Structural biology of the cell adhesion protein CD2: from molecular recognition to protein folding and design. Curr Protein Pept Sci  2003; 4(5): 367-73.
[http://dx.doi.org/10.2174/1389203033487063] [PMID: 14529530] 
[59] 
Cooley S, Burns LJ, Repka T, Miller JS. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu. Exp Hematol  1999; 27(10): 1533-41.
[http://dx.doi.org/10.1016/S0301-472X(99)00089-2] [PMID: 10517495] 
[60] 
Liu LL, Landskron J, Ask EH, et al. Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans. Cell Rep  2016; 15(5): 1088-99.
[http://dx.doi.org/10.1016/j.celrep.2016.04.005] [PMID: 27117418] 
[61] 
Grier JT. A role for CD16 (FcgammaRIIIA) in natural killer cell-mediated spontaneous cytotoxicity identified via a human immunodeficiency-causing germline mutation Dissertations available from ProQuest AAI3550957 2012.
[62] 
Li J, Nishizawa K, An W, et al. A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion. EMBO J  1998; 17(24): 7320-36.
[http://dx.doi.org/10.1093/emboj/17.24.7320] [PMID: 9857189] 
[63] 
Nishizawa K, Freund C, Li J, Wagner G, Reinherz EL. Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation. Proc Natl Acad Sci USA  1998; 95(25): 14897-902.
[http://dx.doi.org/10.1073/pnas.95.25.14897] [PMID: 9843987] 
[64] 
King PD, Sadra A, Han A, et al. CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. Int Immunol  1996; 8(11): 1707-14.
[http://dx.doi.org/10.1093/intimm/8.11.1707] [PMID: 8943565] 
[65] 
Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB. The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2. J Exp Med  1996; 183(1): 169-78.
[http://dx.doi.org/10.1084/jem.183.1.169] [PMID: 8551220] 
[66] 
Hutchcroft JE, Slavik JM, Lin H, Watanabe T, Bierer BE. Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells: differential signaling through CD3 and the costimulatory receptors CD2 and CD28. J Immunol  1998; 161(9): 4506-12.
[PMID: 9794375] 
[67] 
Hahn WC, Menu E, Bothwell AL, Sims PJ, Bierer BE. Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Science  1992; 256(5065): 1805-7.
[http://dx.doi.org/10.1126/science.1377404] [PMID: 1377404] 
[68] 
Deckert M, Kubar J, Zoccola D, et al. CD59 molecule: a second ligand for CD2 in T cell adhesion. Eur J Immunol  1992; 22(11): 2943-7.
[http://dx.doi.org/10.1002/eji.1830221128] [PMID: 1385156] 
[69] 
Nishikori M, Kitawaki T, Tashima M, Shimazu Y, Mori M, et al. Diminished CD2 Expression in T Cells Permits Tumor Immune Escape. J Clin Cell Immunol  2016; 7: 406.
[http://dx.doi.org/10.4172/2155-9899.1000406] 
[70] 
Harcharik S, Bernardo S, Moskalenko M, et al. Defining the role of CD2 in disease progression and overall survival among patients with completely resected stage-II to -III cutaneous melanoma. J Am Acad Dermatol  2014; 70(6): 1036-44.
[http://dx.doi.org/10.1016/j.jaad.2014.01.914] [PMID: 24698703] 
[71] 
Killeen N, Stuart SG, Littman DR. Development and function of T cells in mice with a disrupted CD2 gene. EMBO J  1992; 11(12): 4329-36.
[http://dx.doi.org/10.1002/j.1460-2075.1992.tb05532.x] [PMID: 1358605] 
[72] 
Kulkarni S, Martin MP, Carrington M. The Yin and Yang of HLA and KIR in human disease. Semin Immunol  2008; 20(6): 343-52.
[http://dx.doi.org/10.1016/j.smim.2008.06.003] [PMID: 18635379] 
[73] 
Williams F, Meenagh A, Sleator C, et al. Activating killer cell immunoglobulin-like receptor gene KIR2DS1 is associated with psoriatic arthritis. Hum Immunol  2005; 66(7): 836-41.
[http://dx.doi.org/10.1016/j.humimm.2005.04.005] [PMID: 16112031] 
[74] 
Mason LH, Willette-Brown J, Taylor LS, McVicar DW. Regulation of Ly49D/DAP12 signal transduction by Src-family kinases and CD45. J Immunol  2006; 176(11): 6615-23.
[http://dx.doi.org/10.4049/jimmunol.176.11.6615] [PMID: 16709819] 
[75] 
Wu J, Cherwinski H, Spies T, Phillips JH, Lanier LL. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J Exp Med  2000; 192(7): 1059-68.
[http://dx.doi.org/10.1084/jem.192.7.1059] [PMID: 11015446] 
[76] 
Lanier LL, Bakker AB. The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol Today  2000; 21(12): 611-4.
[http://dx.doi.org/10.1016/S0167-5699(00)01745-X] [PMID: 11114420] 
[77] 
Maghazachi AA. Insights into seven and single transmembrane-spanning domain receptors and their signaling pathways in human natural killer cells. Pharmacol Rev  2005; 57(3): 339-57.
[http://dx.doi.org/10.1124/pr.57.3.5] [PMID: 16109839] 
[78] 
Upshaw JL, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ. The isoforms of phospholipase C-gamma are differentially used by distinct human NK activating receptors. J Immunol  2005; 175(1): 213-8.
[http://dx.doi.org/10.4049/jimmunol.175.1.213] [PMID: 15972651] 
[79] 
Caraux A, Kim N, Bell SE, et al. Phospholipase C-gamma2 is essential for NK cell cytotoxicity and innate immunity to malignant and virally infected cells. Blood  2006; 107(3): 994-1002.
[http://dx.doi.org/10.1182/blood-2005-06-2428] [PMID: 16204312] 
[80] 
Sasahara Y, Rachid R, Byrne MJ, et al. Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation. Mol Cell  2002; 10(6): 1269-81.
[http://dx.doi.org/10.1016/S1097-2765(02)00728-1] [PMID: 12504004] 
[81] 
Villalba M. What came first: PKCtheta or the immune synapse? Arch Immunol Ther Exp (Warsz)  2004; 52(1): 6-12.
[PMID: 15053228] 
[82] 
Antón IM, Jones GE. WIP: a multifunctional protein involved in actin cytoskeleton regulation. Eur J Cell Biol  2006; 85(3-4): 295-304.
[http://dx.doi.org/10.1016/j.ejcb.2005.08.004] [PMID: 16546573] 
[83] 
Krzewski K, Chen X, Orange JS, Strominger JL. Formation of a WIP-, WASp-, actin-, and myosin IIA-containing multiprotein complex in activated NK cells and its alteration by KIR inhibitory signaling The Journal of cell biology 2006.
[84] 
Moon KD, Post CB, Durden DL, et al. Molecular basis for a direct interaction between the Syk protein-tyrosine kinase and phosphoinositide 3-kinase The Journal of biological chemistry 2005.
[85] 
Jiang K, Zhong B, Gilvary DL, et al. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Nat Immunol  2000; 1(5): 419-25.
[http://dx.doi.org/10.1038/80859] [PMID: 11062502] 
[86] 
Jiang K, Zhong B, Gilvary DL, et al. Syk regulation of phosphoinositide 3-kinase-dependent NK cell function. J Immunol  2002; 168(7): 3155-64.
[http://dx.doi.org/10.4049/jimmunol.168.7.3155] [PMID: 11907067] 
[87] 
Yusa S, Catina TL, Campbell KS. SHP-1- and phosphotyrosine-independent inhibitory signaling by a killer cell Ig-like receptor cytoplasmic domain in human NK cells. J Immunol  2002; 168(10): 5047-57.
[http://dx.doi.org/10.4049/jimmunol.168.10.5047] [PMID: 11994457] 
[88] 
Ashouri E, Dabbaghmanesh MH, Rowhanirad S, Bakhshayeshkaram M, Ranjbar Omrani G, Ghaderi A. Activating KIR2DS5 receptor is a risk for thyroid cancer. Hum Immunol  2012; 73(10): 1017-22.
[http://dx.doi.org/10.1016/j.humimm.2012.07.325] [PMID: 22836040] 
[89] 
Ghanadi K, Shayanrad B, Ahmadi SA, Shahsavar F, Eliasy H, Hossein E. Colorectal cancer and the KIR genes in the human genome: A meta-analysis. Genom Data  2016; 10: 118-26.
[http://dx.doi.org/10.1016/j.gdata.2016.10.010] [PMID: 27843767] 
[90] 
Thiruchelvam-Kyle L, Hoelsbrekken SE, Saether PC, et al. The Activating Human NK Cell Receptor KIR2DS2 Recognizes a β2-Microglobulin-Independent Ligand on Cancer Cells. J Immunol  2017; 198(7): 2556-67.
[http://dx.doi.org/10.4049/jimmunol.1600930] [PMID: 28202613] 
[91] 
Sivori S, Carlomagno S, Falco M, Romeo E, Moretta L, Moretta A. Natural killer cells expressing the KIR2DS1-activating receptor efficiently kill T-cell blasts and dendritic cells: implications in haploidentical HSCT. Blood  2011; 117(16): 4284-92.
[http://dx.doi.org/10.1182/blood-2010-10-316125] [PMID: 21355085] 
[92] 
Venstrom JM, Dupont B, Hsu KC, et al. Donor activating KIR2DS1 in leukemia. N Engl J Med  2014; 371(21): 2042.
[http://dx.doi.org/10.1056/NEJMc1411443] [PMID: 25409391] 
[93] 
Ivarsson MA, Michaëlsson J, Fauriat C. Activating killer cell Ig-like receptors in health and disease. Front Immunol  2014; 5: 184.
[http://dx.doi.org/10.3389/fimmu.2014.00184] [PMID: 24795726] 
[94] 
Shiratori I, Ogasawara K, Saito T, Lanier LL, Arase H. Activation of natural killer cells and dendritic cells upon recognition of a novel CD99-like ligand by paired immunoglobulin-like type 2 receptor. J Exp Med  2004; 199(4): 525-33.
[http://dx.doi.org/10.1084/jem.20031885] [PMID: 14970179] 
[95] 
Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition. Immunology  2005; 115(4): 433-40.
[http://dx.doi.org/10.1111/j.1365-2567.2005.02177.x] [PMID: 16011512] 
[96] 
Ma G, Pan PY, Eisenstein S, et al. Paired immunoglobin-like receptor-B regulates the suppressive function and fate of myeloid-derived suppressor cells. Immunity  2011; 34(3): 385-95.
[http://dx.doi.org/10.1016/j.immuni.2011.02.004] [PMID: 21376641] 
[97] 
Maeda A, Scharenberg AM, Tsukada S, Bolen JB, Kinet JP, Kurosaki T. Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1. Oncogene  1999; 18(14): 2291-7.
[http://dx.doi.org/10.1038/sj.onc.1202552] [PMID: 10327049] 
[98] 
Wang J, Shiratori I, Satoh T, Lanier LL, Arase H. An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired Ig-like type 2 receptor (PILR). J Immunol  2008; 180(3): 1686-93.
[http://dx.doi.org/10.4049/jimmunol.180.3.1686] [PMID: 18209065] 
[99] 
Chan CJ, Martinet L, Gilfillan S, et al. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol  2014; 15(5): 431-8.
[http://dx.doi.org/10.1038/ni.2850] [PMID: 24658051] 
[100] 
Tahara-Hanaoka S, Shibuya K, Onoda Y, et al. Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). Int Immunol  2004; 16(4): 533-8.
[http://dx.doi.org/10.1093/intimm/dxh059] [PMID: 15039383] 
[101] 
Du X, de Almeida P, Manieri N, et al. CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1. Proc Natl Acad Sci USA  2018; 115(50): E11731-40.
[http://dx.doi.org/10.1073/pnas.1814052115] [PMID: 30504141] 
[102] 
Shibuya A, Lanier LL, Phillips JH. Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor. J Immunol  1998; 161(4): 1671-6.
[PMID: 9712030] 
[103] 
Lozano E, Joller N, Cao Y, Kuchroo VK, Hafler DA. The CD226/CD155 interaction regulates the proinflammatory (Th1/Th17)/anti-inflammatory (Th2) balance in humans. J Immunol  2013; 191(7): 3673-80.
[http://dx.doi.org/10.4049/jimmunol.1300945] [PMID: 23980210] 
[104] 
Bachelet I, Munitz A, Mankutad D, Levi-Schaffer F. Mast cell costimulation by CD226/CD112 (DNAM-1/Nectin-2): a novel interface in the allergic process J Biol Chem  2006; 281(37): 27190-6.
[105] 
Shibuya A, Campbell D, Hannum C, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity  1996; 4(6): 573-81.
[http://dx.doi.org/10.1016/S1074-7613(00)70060-4] [PMID: 8673704] 
[106] 
Freud AG, Zhao S, Wei S, et al. Expression of the activating receptor, NKp46 (CD335), in human natural killer and T-cell neoplasia. Am J Clin Pathol  2013; 140(6): 853-66.
[http://dx.doi.org/10.1309/AJCPWGG69MCZOWMM] [PMID: 24225754] 
[107] 
Augugliaro R, Parolini S, Castriconi R, et al. Selective cross-talk among natural cytotoxicity receptors in human natural killer cells. Eur J Immunol  2003; 33(5): 1235-41.
[http://dx.doi.org/10.1002/eji.200323896] [PMID: 12731048] 
[108] 
Moretta A, Bottino C, Vitale M, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol  2001; 19: 197-223.
[http://dx.doi.org/10.1146/annurev.immunol.19.1.197] [PMID: 11244035] 
[109] 
Sivori S, Vitale M, Morelli L, et al. p46, a novel natural killer cell-specific surface molecule that mediates cell activation. J Exp Med  1997; 186(7): 1129-36.
[http://dx.doi.org/10.1084/jem.186.7.1129] [PMID: 9314561] 
[110] 
Pessino A, Sivori S, Bottino C, et al. Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J Exp Med  1998; 188(5): 953-60.
[http://dx.doi.org/10.1084/jem.188.5.953] [PMID: 9730896] 
[111] 
Foster CE, Colonna M, Sun PD. Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors. J Biol Chem  2003; 278(46): 46081-6.
[http://dx.doi.org/10.1074/jbc.M308491200] [PMID: 12960161] 
[112] 
Ponassi M, Cantoni C, Biassoni R, et al. Structure of the human NK cell triggering receptor NKp46 ectodomain. Biochem Biophys Res Commun  2003; 309(2): 317-23.
[http://dx.doi.org/10.1016/j.bbrc.2003.08.007] [PMID: 12951052] 
[113] 
Rodewald HR, Arulanandam AR, Koyasu S, Reinherz EL. The high affinity Fc epsilon receptor gamma subunit (Fc epsilon RI gamma) facilitates T cell receptor expression and antigen/major histocompatibility complex-driven signaling in the absence of CD3 zeta and CD3 eta. J Biol Chem  1991; 266(24): 15974-8.
[PMID: 1714902] 
[114] 
Johnson WC, Bastos RG, Davis WC, Goff WL, Davis B, Will LG. Bovine WC1(-) gammadeltaT cells incubated with IL-15 express the natural cytotoxicity receptor CD335 (NKp46) and produce IFN-γ in response to exogenous IL-12 and IL-18. Dev Comp Immunol  2008; 32(8): 1002-10.
[http://dx.doi.org/10.1016/j.dci.2008.01.011] [PMID: 18329100] 
[115] 
Glasner A, Ghadially H, Gur C, et al. Recognition and prevention of tumor metastasis by the NK receptor NKp46/NCR1. J Immunol  2012; 188(6): 2509-15.
[http://dx.doi.org/10.4049/jimmunol.1102461] [PMID: 22308311] 
[116] 
Merzoug LB, Marie S, Satoh-Takayama N, et al. Conditional ablation of NKp46+ cells using a novel Ncr1(greenCre) mouse strain: NK cells are essential for protection against pulmonary B16 metastases. Eur J Immunol  2014; 44(11): 3380-91.
[http://dx.doi.org/10.1002/eji.201444643] [PMID: 25142413] 
[117] 
Allcock RJ, Barrow AD, Forbes S, Beck S, Trowsdale J. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Eur J Immunol  2003; 33(2): 567-77.
[http://dx.doi.org/10.1002/immu.200310033] [PMID: 12645956] 
[118] 
Cantoni C, Bottino C, Vitale M, et al. NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. J Exp Med  1999; 189(5): 787-96.
[http://dx.doi.org/10.1084/jem.189.5.787] [PMID: 10049942] 
[119] 
Cantoni C, Ponassi M, Biassoni R, et al. Crystallization and preliminary crystallographic characterization of the extracellular Ig-like domain of human natural killer cell activating receptor NKp44. Acta Crystallogr D Biol Crystallogr  2002; 58(Pt 10 Pt 2): 1843-5.
[http://dx.doi.org/10.1107/S0907444902012325] [PMID: 12351833] 
[120] 
Cantoni C, Ponassi M, Biassoni R, et al. The three-dimensional structure of the human NK cell receptor NKp44, a triggering partner in natural cytotoxicity. Structure  2003; 11(6): 725-34.
[http://dx.doi.org/10.1016/S0969-2126(03)00095-9] [PMID: 12791260] 
[121] 
Hershkovitz O, Jivov S, Bloushtain N, et al. Characterization of the recognition of tumor cells by the natural cytotoxicity receptor, NKp44. Biochemistry  2007; 46(25): 7426-36.
[http://dx.doi.org/10.1021/bi7000455] [PMID: 17536787] 
[122] 
Vitale M, Della Chiesa M, Carlomagno S, et al. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Blood  2005; 106(2): 566-71.
[http://dx.doi.org/10.1182/blood-2004-10-4035] [PMID: 15784725] 
[123] 
Pende D, Parolini S, Pessino A, et al. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med  1999; 190(10): 1505-16.
[http://dx.doi.org/10.1084/jem.190.10.1505] [PMID: 10562324] 
[124] 
Textor S, Bossler F, Henrich KO, et al. The proto-oncogene Myc drives expression of the NK cell-activating NKp30 ligand B7-H6 in tumor cells. OncoImmunology  2016; 5(7)e1116674
[http://dx.doi.org/10.1080/2162402X.2015.1116674] [PMID: 27622013] 
[125] 
Vitale M, Bottino C, Sivori S, et al. NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis. J Exp Med  1998; 187(12): 2065-72.
[http://dx.doi.org/10.1084/jem.187.12.2065] [PMID: 9625766] 
[126] 
Warren HS, Jones AL, Freeman C, Bettadapura J, Parish CR. Evidence That the Cellular Ligand for the Human NK Cell Activation Receptor NKp30 Is Not a Heparan Sulfate Glycosaminoglycan The Journal of Immunology 2005.
[127] 
Joyce MG, Tran P, Zhuravleva MA, Jaw J, Colonna M, Sun PD. Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site. Proc Natl Acad Sci USA  2011; 108(15): 6223-8.
[http://dx.doi.org/10.1073/pnas.1100622108] [PMID: 21444796] 
[128] 
Chlewicki LK, Velikovsky CA, Balakrishnan V, Mariuzza RA, Kumar V. Molecular basis of the dual functions of 2B4 (CD244). J Immunol  2008; 180(12): 8159-67.
[http://dx.doi.org/10.4049/jimmunol.180.12.8159] [PMID: 18523281] 
[129] 
Bryceson YT, March ME, Ljunggren HG, Long EO. Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood  2006; 107(1): 159-66.
[http://dx.doi.org/10.1182/blood-2005-04-1351] [PMID: 16150947] 
[130] 
Kumaresan PR, Mathew PA. Structure of the human natural killer cell receptor 2B4 gene and identification of a novel alternative transcript. Immunogenetics  2000; 51(11): 987-92.
[http://dx.doi.org/10.1007/s002510000237] [PMID: 11003394] 
[131] 
Mathew SO, Rao KK, Kim JR, Bambard ND, Mathew PA. Functional role of human NK cell receptor 2B4 (CD244) isoforms. Eur J Immunol  2009; 39(6): 1632-41.
[http://dx.doi.org/10.1002/eji.200838733] [PMID: 19499526] 
[132] 
Latour S, Roncagalli R, Chen R, et al. Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation. Nat Cell Biol  2003; 5(2): 149-54.
[http://dx.doi.org/10.1038/ncb919] [PMID: 12545173] 
[133] 
Dong Z, Davidson D, Pérez-Quintero LA, Kurosaki T, Swat W, Veillette A. The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells. Immunity  2012; 36(6): 974-85.
[http://dx.doi.org/10.1016/j.immuni.2012.03.023] [PMID: 22683124] 
[134] 
Veillette A, Dong Z, Pérez-Quintero LA, Zhong MC, Cruz-Munoz ME. Importance and mechanism of ‘switch’ function of SAP family adapters. Immunol Rev  2009; 232(1): 229-39.
[http://dx.doi.org/10.1111/j.1600-065X.2009.00824.x] [PMID: 19909367] 
[135] 
Tangye SG, Cherwinski H, Lanier LL, Phillips JH. 2B4-mediated activation of human natural killer cells. Mol Immunol  2000; 37(9): 493-501.
[http://dx.doi.org/10.1016/S0161-5890(00)00076-6] [PMID: 11163399] 
[136] 
Bauer S, Groh V, Wu J, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science  1999; 285(5428): 727-9.
[http://dx.doi.org/10.1126/science.285.5428.727] [PMID: 10426993] 
[137] 
Yabe T, McSherry C, Bach FH, et al. A multigene family on human chromosome 12 encodes natural killer-cell lectins. Immunogenetics  1993; 37(6): 455-60.
[http://dx.doi.org/10.1007/BF00222470] [PMID: 8436421] 
[138] 
Houchins JP, Yabe T, McSherry C, Bach FH. DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J Exp Med  1991; 173(4): 1017-20.
[http://dx.doi.org/10.1084/jem.173.4.1017] [PMID: 2007850] 
[139] 
Lanier LL. NK cell recognition. Annu Rev Immunol  2005; 23: 225-74.
[http://dx.doi.org/10.1146/annurev.immunol.23.021704.115526] [PMID: 15771571] 
[140] 
Iwaszko M, Bogunia-Kubik K. Clinical significance of the HLA-E and CD94/NKG2 interaction. Arch Immunol Ther Exp (Warsz)  2011; 59(5): 353-67.
[http://dx.doi.org/10.1007/s00005-011-0137-y] [PMID: 21800130] 
[141] 
Ding Y, Sumitran S, Holgersson J. Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells. Scand J Immunol  1999; 49(5): 459-65.
[http://dx.doi.org/10.1046/j.1365-3083.1999.00566.x] [PMID: 10320637] 
[142] 
Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol  1996; 157(11): 4741-5.
[PMID: 8943374] 
[143] 
Braud VM, Allan DS, O’Callaghan CA, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature  1998; 391(6669): 795-9.
[http://dx.doi.org/10.1038/35869] [PMID: 9486650] 
[144] 
Rölle A, Pollmann J, Ewen EM, et al. IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. J Clin Invest  2014; 124(12): 5305-16.
[http://dx.doi.org/10.1172/JCI77440] [PMID: 25384219] 
[145] 
Malmberg KJ, Beziat V, Ljunggren HG. Spotlight on NKG2C and the human NK-cell response to CMV infection. Eur J Immunol  2012; 42(12): 3141-5.
[http://dx.doi.org/10.1002/eji.201243050] [PMID: 23255011] 
[146] 
Kordelas L. Nina-Kristin Steckel, Peter A. Horn, Dietrich W. Beelen, and Vera Rebmann (2016). The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease. Int J Mol Sci  1797; 17(11)
[http://dx.doi.org/10.3390/ijms17111797] 
[147] 
Upshaw JL, Arneson LN, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ. NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nat Immunol  2006; 7(5): 524-32.
[http://dx.doi.org/10.1038/ni1325] [PMID: 16582911] 
[148] 
Li P, Morris DL, Willcox BE, Steinle A, Spies T, Strong RK. Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA. Nat Immunol  2001; 2(5): 443-51.
[http://dx.doi.org/10.1038/87757] [PMID: 11323699] 
[149] 
Garrity D, Call ME, Feng J, Wucherpfennig KW. The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure. Proc Natl Acad Sci USA  2005; 102(21): 7641-6.
[http://dx.doi.org/10.1073/pnas.0502439102] [PMID: 15894612] 
[150] 
Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature  2005; 436(7054): 1186-90.
[http://dx.doi.org/10.1038/nature03884] [PMID: 15995699] 
[151] 
Raulet DH, Gasser S, Gowen BG, Deng W, Jung H. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol  2013; 31(1): 413-41.
[http://dx.doi.org/10.1146/annurev-immunol-032712-095951] [PMID: 23298206] 
[152] 
Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M. NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation. Nat Immunol  2002; 3(12): 1150-5.
[http://dx.doi.org/10.1038/ni857] [PMID: 12426564] 
[153] 
Segovis CM, Schoon RA, Dick CJ, Nacusi LP, Leibson PJ, Billadeau DD. PI3K links NKG2D signaling to a CrkL pathway involved in natural killer cell adhesion, polarity, and granule secretion. J Immunol  2009; 182(11): 6933-42.
[http://dx.doi.org/10.4049/jimmunol.0803840] [PMID: 19454690] 
[154] 
Jamieson AM, Diefenbach A, McMahon CW, Xiong N, Carlyle JR, Raulet DH. The role of the NKG2D immunoreceptor in immune cell activation and natural killing. Immunity  2002; 17(1): 19-29.
[http://dx.doi.org/10.1016/S1074-7613(02)00333-3] [PMID: 12150888] 
[155] 
Zafirova B, Wensveen FM, Gulin M, Polić B. Regulation of immune cell function and differentiation by the NKG2D receptor. Cell Mol Life Sci  2011; 68(21): 3519-29.
[http://dx.doi.org/10.1007/s00018-011-0797-0] [PMID: 21898152] 
[156] 
Orbelyan GA, Tang F, Sally B, et al. Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12. J Immunol  2014; 193(2): 610-6.
[http://dx.doi.org/10.4049/jimmunol.1400556] [PMID: 24935923] 
[157] 
Nakata S, Imagawa A, Miyata Y, et al. Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes. Immunol Lett  2013; 156(1-2): 149-55.
[http://dx.doi.org/10.1016/j.imlet.2013.10.004] [PMID: 24177169] 
[158] 
Rückrich T, Steinle A. Attenuated Natural Killer (NK) cell activation through NKp80 is due to an anomalous hemi-immunoreceptor-tyrosine-based activation motif (hemITAM) with impaired Syk kinase recruitment capacity J Biol Chem  2013; 288(24): 17725-33.
[159] 
Vitale M, Falco M, Castriconi R, et al. Identification of NKp80, a novel triggering molecule expressed by human NK cells. Eur J Immunol  2001; 31(1): 233-42.
[http://dx.doi.org/10.1002/1521-4141(200101)31:1<233::AID-IMMU233>3.0.CO;2-4] [PMID: 11265639] 
[160] 
Luis SA, Bauer B, Vogler I, Leibelt S. C-type lectin-like NK CELL-encoded immunoreceptors NKp80 and NKp65 are selectively expressed by human innate lymphocyte subsets, uniquely signal via hemITAMs and facilitate tissue-specific immunosurveillance via their genetically linked ligands AICL and KACL J Immunol  2016; 196(1 Supplement): 202-7.
[161] 
Barbora Kalousková, Nový Jiří, Bláha Jan, Vaněk Ondřej. Preparation of human NK cell activation receptor NKp80 and its ligand AICL Czech Science Foundation (15-15181S), Charles University (UNCE 204025/2012, SVV 260079/2014) 2016.
[162] 
Minami Y, Kono T, Miyazaki T, Taniguchi T. The IL-2 receptor complex: its structure, function, and target genes. Annu Rev Immunol  1993; 11: 245-68.
[http://dx.doi.org/10.1146/annurev.iy.11.040193.001333] [PMID: 8476561] 
[163] 
Wang KS, Frank DA, Ritz J. Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood  2000; 95(10): 3183-90.
[http://dx.doi.org/10.1182/blood.V95.10.3183] [PMID: 10807786] 
[164] 
Mulloy JC, Crownley RW, Fullen J, Leonard WJ, Franchini G. The human T-cell leukemia/lymphotropic virus type 1 p12I proteins bind the interleukin-2 receptor beta and gammac chains and affects their expression on the cell surface. J Virol  1996; 70(6): 3599-605.
[http://dx.doi.org/10.1128/JVI.70.6.3599-3605.1996] [PMID: 8648694] 
[165] 
Goudy K, Aydin D, Barzaghi F, et al. Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity. Clin Immunol  2013; 146(3): 248-61.
[http://dx.doi.org/10.1016/j.clim.2013.01.004] [PMID: 23416241] 
[166] 
Suwa H, Tanaka T, Kitamura F, Shiohara T, Kuida K, Miyasaka M. Dysregulated expression of the IL-2 receptor beta-chain abrogates development of NK cells and Thy-1+ dendritic epidermal cells in transgenic mice. Int Immunol  1995; 7(9): 1441-9.
[http://dx.doi.org/10.1093/intimm/7.9.1441] [PMID: 7495752] 
[167] 
Lowe CE, Cooper JD, Brusko T, et al. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet  2007; 39(9): 1074-82.
[http://dx.doi.org/10.1038/ng2102] [PMID: 17676041] 
[168] 
Russell SM, Keegan AD, Harada N, et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science  1993; 262(5141): 1880-3.
[http://dx.doi.org/10.1126/science.8266078] [PMID: 8266078] 
[169] 
Noguchi M, Nakamura Y, Russell SM, et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science  1993; 262(5141): 1877-80.
[http://dx.doi.org/10.1126/science.8266077] [PMID: 8266077] 
[170] 
Giri JG, Kumaki S, Ahdieh M, et al. Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. EMBO J  1995; 14(15): 3654-63.
[http://dx.doi.org/10.1002/j.1460-2075.1995.tb00035.x] [PMID: 7641685] 
[171] 
Bulanova E, Budagian V, Pohl T, et al. The IL-15R α chain signals through association with Syk in human B cells. J Immunol  2001; 167(11): 6292-302.
[http://dx.doi.org/10.4049/jimmunol.167.11.6292] [PMID: 11714793] 
[172] 
Tagaya Y, Burton DJ, Miyamoto Y, Thomas AW. Identification of a novel receptor/signal transduction pathway for IL-15/T in mast cells BOJ  1996; 15(18): 4928-39.
[173] 
Wu TS, Lee JM, Lai YG, et al. Reduced expression of Bcl-2 in CD8+ T cells deficient in the IL-15 receptor alpha-chain. J Immunol  2002; 168(2): 705-12.
[http://dx.doi.org/10.4049/jimmunol.168.2.705] [PMID: 11777964] 
[174] 
Colpitts SL. Lynn Puddington and Leo Lefrançois IL. Proceedings of the National Academy of Sciences of the United States of America.  9692-7.
[175] 
Tsuji-Takayama K, Matsumoto S, Koide K, et al. Interleukin-18 induces activation and association of p56(lck) and MAPK in a murine TH1 clone. Biochem Biophys Res Commun  1997; 237(1): 126-30.
[http://dx.doi.org/10.1006/bbrc.1997.7099] [PMID: 9266843] 
[176] 
Jia H, Liu J, Han B. Reviews of Interleukin-37: functions, receptors, and roles in diseases. BioMed Res Int  2018; 20183058640
[http://dx.doi.org/10.1155/2018/3058640] [PMID: 29805973] 
[177] 
Garlanda C, Anders HJ, Mantovani A. TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization. Trends Immunol  2009; 30(9): 439-46.
[http://dx.doi.org/10.1016/j.it.2009.06.001] [PMID: 19699681] 
[178] 
Julie C, Tessmer MS, Hoebe K, et al. Priming of Natural Killer cells by Interleukin-18. J Immunol  2008; 181(3): 1627-31.
[http://dx.doi.org/10.4049/jimmunol.181.3.1627] [PMID: 18641298] 
[179] 
Senju H, Kumagai A, Nakamura Y, et al. Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. Int J Biol Sci  2018; 14(3): 331-40.
[http://dx.doi.org/10.7150/ijbs.22809] [PMID: 29559850] 
[180] 
Srivastava S, Pelloso D, Feng H, et al. Effects of interleukin-18 on natural killer cells: costimulation of activation through Fc receptors for immunoglobulin. Cancer Immunol Immunother  2013; 62(6): 1073-82.
[http://dx.doi.org/10.1007/s00262-013-1403-0] [PMID: 23604103] 
[181] 
Presky DH, Yang H, Minetti LJ, et al. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci USA  1996; 93(24): 14002-7.
[http://dx.doi.org/10.1073/pnas.93.24.14002] [PMID: 8943050] 
[182] 
Parham C, Chirica M, Timans J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol  2002; 168(11): 5699-708.
[http://dx.doi.org/10.4049/jimmunol.168.11.5699] [PMID: 12023369] 
[183] 
Helena A. Jonsson, Wayne M Yokoyama. Natural Killer Cell Tolerance Licensing and Other Mechanisms Adv Immunol  2009; 101: 27-79.
[184] 
Yokoyama WM, Kim S. Licensing of natural killer cells by self-major histocompatibility complex class I. Immunol Rev  2006; 214: 143-54.
[http://dx.doi.org/10.1111/j.1600-065X.2006.00458.x] [PMID: 17100882] 
[185] 
He Y, Tian Z. NK cell education via nonclassical MHC and non-MHC ligands. Cell Mol Immunol  2017; 14(4): 321-30.
[http://dx.doi.org/10.1038/cmi.2016.26] [PMID: 27264685] 
[186] 
Ebihara T, Jonsson AH, Yokoyama WM. Natural killer cell licensing in mice with inducible expression of MHC class I. Proc Natl Acad Sci USA  2013; 110(45): E4232-7.
[http://dx.doi.org/10.1073/pnas.1318255110] [PMID: 24145414] 
[187] 
Rose MJ, Brooks AG, Stewart LA, Nguyen TH, Schwarer AP. Killer Ig-like receptor ligand mismatch directs NK cell expansion in vitro. J Immunol  2009; 183(7): 4502-8.
[http://dx.doi.org/10.4049/jimmunol.0803323] [PMID: 19748981] 
[188] 
Hasenkamp J, Borgerding A, Uhrberg M, et al. Self-tolerance of human natural killer cells lacking self-HLA-specific inhibitory receptors. Scand J Immunol  2008; 67(3): 218-29.
[http://dx.doi.org/10.1111/j.1365-3083.2007.02058.x] [PMID: 18226015] 
[189] 
Carotta S. Targeting NK Cells for Anticancer Immunotherapy: Clinical and Preclinical Approaches. Front Immunol  2016; 7: 152.
[http://dx.doi.org/10.3389/fimmu.2016.00152] [PMID: 27148271] 
[190] 
Sun H, Sun C. The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy. Front Immunol  2019; 10: 2354.
[http://dx.doi.org/10.3389/fimmu.2019.02354] [PMID: 31681269] 
[191] 
Bracci L, Schiavoni G, Sistigu A, Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ  2014; 21(1): 15-25.
[http://dx.doi.org/10.1038/cdd.2013.67] [PMID: 23787994] 
[192] 
Childs RW, Carlsten M. Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens. Nat Rev Drug Discov  2015; 14(7): 487-98.
[http://dx.doi.org/10.1038/nrd4506] [PMID: 26000725] 
[193] 
Waldmann TA, Dubois S, Miljkovic MD, Conlon KC. IL-15 in the Combination Immunotherapy of Cancer. Front Immunol  2020; 11: 868.
[http://dx.doi.org/10.3389/fimmu.2020.00868] [PMID: 32508818] 
[194] 
Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol  2014; 15(1): 69-77.
[http://dx.doi.org/10.1016/S1470-2045(13)70551-5] [PMID: 24332512] 
[195] 
Ndhlovu LC, Lopez-Vergès S, Barbour JD, et al. Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood  2012; 119(16): 3734-43.
[http://dx.doi.org/10.1182/blood-2011-11-392951] [PMID: 22383801] 
[196] 
Lo Monaco E, Tremante E, Cerboni C, et al. Human leukocyte antigen E contributes to protect tumor cells from lysis by natural killer cells. Neoplasia  2011; 13(9): 822-30.
[http://dx.doi.org/10.1593/neo.101684] [PMID: 21969815] 
[197] 
Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci USA  2009; 106(42): 17858-63.
[http://dx.doi.org/10.1073/pnas.0903474106] [PMID: 19815499] 
[198] 
Xu F, Sunderland A, Zhou Y, Schulick RD, Edil BH, Zhu Y. Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions. Cancer Immunol Immunother  2017; 66(10): 1367-75.
[http://dx.doi.org/10.1007/s00262-017-2031-x] [PMID: 28623459] 
[199] 
Audenet F, Farkas AM, Anastos H, Galsky MD, Bhardwaj N, Sfakianos JP. Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer. World J Urol  2018; 36(11): 1741-8.
[http://dx.doi.org/10.1007/s00345-018-2359-7] [PMID: 29860605] 
[200] 
Wilson EB, El-Jawhari JJ, Neilson AL, et al. Human tumour immune evasion via TGF-β blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity. PLoS One  2011; 6(9)e22842
[http://dx.doi.org/10.1371/journal.pone.0022842] [PMID: 21909397] 
[201] 
Romagné F, André P, Spee P, et al. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood  2009; 114(13): 2667-77.
[http://dx.doi.org/10.1182/blood-2009-02-206532] [PMID: 19553639] 
[202] 
Vahlne G, Lindholm K, Meier A, et al. In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: maintained tolerance to normal cells even in the presence of IL-2. Eur J Immunol  2010; 40(3): 813-23.
[http://dx.doi.org/10.1002/eji.200939755] [PMID: 20039300] 
[203] 
Blake SJ, Stannard K, Liu J, et al. Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy. Cancer Discov  2016; 6(4): 446-59.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0944] [PMID: 26787820] 
[204] 
Xu L, Huang Y, Tan L, et al. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. Int Immunopharmacol  2015; 29(2): 635-41.
[http://dx.doi.org/10.1016/j.intimp.2015.09.017] [PMID: 26428847] 
[205] 
da Silva IP, Gallois A, Jimenez-Baranda S, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res  2014; 2(5): 410-22.
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0171] [PMID: 24795354] 
[206] 
Blackburn SD, Shin H, Haining WN, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol  2009; 10(1): 29-37.
[http://dx.doi.org/10.1038/ni.1679] [PMID: 19043418] 
[207] 
Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity  2016; 44(5): 989-1004.
[http://dx.doi.org/10.1016/j.immuni.2016.05.001] [PMID: 27192565] 
[208] 
Kwon H-J, Kim N, Kim HS. Molecular checkpoints controlling natural killer cell activation and their modulation for cancer immunotherapy. Exp Mol Med  2017; 49(3)e311
[http://dx.doi.org/10.1038/emm.2017.42] [PMID: 28360428] 
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DOI https://dx.doi.org/10.2174/1389450121666200910160929	Print ISSN 1389-4501
Publisher Name Bentham Science Publisher	Online ISSN 1873-5592
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