Expression of ligands for activating natural killer cell receptors on cell lines commonly used to assess natural killer cell function
Tóm tắt
Natural killer cell responses to virally-infected or transformed cells depend on the integration of signals received through inhibitory and activating natural killer cell receptors. Human Leukocyte Antigen null cells are used in vitro to stimulate natural killer cell activation through missing-self mechanisms. On the other hand, CEM.NKr.CCR5 cells are used to stimulate natural killer cells in an antibody dependent manner since they are resistant to direct killing by natural killer cells. Both K562 and 721.221 cell lines lack surface major histocompatibility compatibility complex class Ia ligands for inhibitory natural killer cell receptors. Previous work comparing natural killer cell stimulation by K562 and 721.221 found that they stimulated different frequencies of natural killer cell functional subsets. We hypothesized that natural killer cell function following K562, 721.221 or CEM.NKr.CCR5 stimulation reflected differences in the expression of ligands for activating natural killer cell receptors. K562 expressed a higher intensity of ligands for Natural Killer G2D and the Natural Cytotoxicity Receptors, which are implicated in triggering natural killer cell cytotoxicity. 721.221 cells expressed a greater number of ligands for activating natural killer cell receptors. 721.221 expressed cluster of differentiation 48, 80 and 86 with a higher mean fluorescence intensity than did K562. The only ligands for activating receptor that were detected on CEM.NKr.CCR5 cells at a high intensity were cluster of differentiation 48, and intercellular adhesion molecule-2. The ligands expressed by K562 engage natural killer cell receptors that induce cytolysis. This is consistent with the elevated contribution that the cluster of differentiation 107a function makes to total K562 induced natural killer cell functionality compared to 721.221 cells. The ligands expressed on 721.221 cells can engage a larger number of activating natural killer cell receptors, which may explain their ability to activate a larger frequency of these cells to become functional and secrete cytokines. The few ligands for activating natural killer cell receptors expressed by CEM.NKr.CCR5 may reduce their ability to activate natural killer cells in an antibody independent manner explaining their relative resistance to direct natural killer cell cytotoxicity.
Tài liệu tham khảo
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10.
Spits H, Bernink JH, Lanier L. NK cells and type 1 innate lymphoid cells: partners in host defense. Nat Immunol. 2016;17(7):758–64.
Spits H, Di Santo JP. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol. 2011;12(1):21–7.
Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13(2):145–9.
Lettau M, Schmidt H, Kabelitz D, Janssen O. Secretory lysosomes and their cargo in T and NK cells. Immunol Lett. 2007;108(1):10–9.
Orange JS. Human natural killer cell deficiencies and susceptibility to infection. Microbes Infect. 2002;4(15):1545–58.
Cheng M, Chen Y, Xiao W, Sun R, Tian Z. NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol. 2013;10(3):230–52.
Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331(6013):44–9.
Fauriat C, Long EO, Ljunggren HG, Bryceson YT. Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood. 2010;115(11):2167–76.
Lanier LL. NK cell recognition. Annu Rev Immunol. 2005;23:225–74.
Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L. Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol. 2012;12(4):239–52.
Klein E, Ben-Bassat H, Neumann H, Ralph P, Zeuthen J, Polliack A, et al. Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia. Int J Cancer. 1976;18(4):421–31.
Lozzio CB, Lozzio BB. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975;45(3):321–34.
Shimizu Y, DeMars R. Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol. 1989;142(9):3320–8.
Bryceson YT, March ME, Ljunggren HG, Long EO. Activation, coactivation, and costimulation of resting human natural killer cells. Immunol Rev. 2006;214:73–91.
Lisovsky I, Isitman G, Bruneau J, Bernard NF. Functional analysis of NK cell subsets activated by 721.221 and K562 HLA-null cells. J Leukoc Biol. 2015;97(4):761–7.
Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285(5428):727–9.
Bottino C, Castriconi R, Pende D, Rivera P, Nanni M, Carnemolla B, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003;198(4):557–67.
Chalupny NJ, Sutherland CL, Lawrence WA, Rein-Weston A, Cosman D. ULBP4 is a novel ligand for human NKG2D. Biochem Biophys Res Commun. 2003;305(1):129–35.
Sandusky MM, Messmer B, Watzl C. Regulation of 2B4 (CD244)-mediated NK cell activation by ligand-induced receptor modulation. Eur J Immunol. 2006;36(12):3268–76.
Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, Fox B, et al. The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med. 2009;206(7):1495–503.
Sanchez-Correa B, Gayoso I, Bergua JM, Casado JG, Morgado S, Solana R, et al. Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol Cell Biol. 2012;90(1):109–15.
Trkola A, Matthews J, Gordon C, Ketas T, Moore JP. A cell line-based neutralization assay for primary human immunodeficiency virus type 1 isolates that use either the CCR5 or the CXCR4 coreceptor. J Virol. 1999;73(11):8966–74.
Lyerly HK, Reed DL, Matthews TJ, Langlois AJ, Ahearne PA, Petteway SR Jr, et al. Anti-GP 120 antibodies from HIV seropositive individuals mediate broadly reactive anti-HIV ADCC. AIDS Res Hum Retrovir. 1987;3(4):409–22.
Howell DN, Andreotti PE, Dawson JR, Cresswell P. Natural killing target antigens as inducers of interferon: studies with an immunoselected, natural killing-resistant human T lymphoblastoid cell line. J Immunol. 1985;134(2):971–6.
Lanier LL, Ruitenberg JJ, Phillips JH. Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J Immunol. 1988;141(10):3478–85.
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.
Cosman D, Mullberg J, Sutherland CL, Chin W, Armitage R, Fanslow W, et al. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity. 2001;14(2):123–33.
Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol. 2001;19:197–223.
Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, et al. p46, a novel natural killer cell-specific surface molecule that mediates cell activation. J Exp Med. 1997;186(7):1129–36.
Vitale M, Bottino C, Sivori S, Sanseverino L, Castriconi R, Marcenaro E, 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.
Pende D, Parolini S, Pessino A, Sivori S, Augugliaro R, Morelli L, 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.
Mandelboim O, Lieberman N, Lev M, Paul L, Arnon TI, Bushkin Y, et al. Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature. 2001;409(6823):1055–60.
Bloushtain N, Qimron U, Bar-Ilan A, Hershkovitz O, Gazit R, Fima E, et al. Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. J Immunol. 2004;173(4):2392–401.
Arnon TI, Lev M, Katz G, Chernobrov Y, Porgador A, Mandelboim O. Recognition of viral hemagglutinins by NKp44 but not by NKp30. Eur J Immunol. 2001;31(9):2680–9.
Kruse PH, Matta J, Ugolini S, Vivier E. Natural cytotoxicity receptors and their ligands. Immunol Cell Biol. 2014;92(3):221–9.
Hecht ML, Rosental B, Horlacher T, Hershkovitz O, De Paz JL, Noti C, et al. Natural cytotoxicity receptors NKp30, NKp44 and NKp46 bind to different heparan sulfate/heparin sequences. J Proteome Res. 2009;8(2):712–20.
Li SS, Kyei SK, Timm-McCann M, Ogbomo H, Jones GJ, Shi M, et al. The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients. Cell Host Microbe. 2013;14(4):387–97.
Li SS, Mody CH. NKp46 is an NK cell fungicidal pattern recognition receptor. Trends Microbiol. 2016;24(12):929–31.
Li SS, Ogbomo H, Mansour MK, Xiang RF, Szabo L, Munro F, et al. Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida. Nat Commun. 2018;9(1):751.
Brown MH, Boles K, van der Merwe PA, Kumar V, Mathew PA, Barclay AN. 2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48. J Exp Med. 1998;188(11):2083–90.
Pende D, Bottino C, Castriconi R, Cantoni C, Marcenaro S, Rivera P, et al. PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol. 2005;42(4):463–9.
Tahara-Hanaoka S, Shibuya K, Onoda Y, Zhang H, Yamazaki S, Miyamoto A, 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.
Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996;4(6):573–81.
Shibuya K, Lanier LL, Phillips JH, Ochs HD, Shimizu K, Nakayama E, et al. Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity. 1999;11(5):615–23.
Gross CC, Brzostowski JA, Liu D, Long EO. Tethering of intercellular adhesion molecule on target cells is required for LFA-1-dependent NK cell adhesion and granule polarization. J Immunol. 2010;185(5):2918–26.
Schleinitz N, March ME, Long EO. Recruitment of activation receptors at inhibitory NK cell immune synapses. PLoS One. 2008;3(9):e3278.
Culley FJ, Johnson M, Evans JH, Kumar S, Crilly R, Casasbuenas J, et al. Natural killer cell signal integration balances synapse symmetry and migration. PLoS Biol. 2009;7(7):e1000159.
Luque I, Reyburn H, Strominger JL. Expression of the CD80 and CD86 molecules enhances cytotoxicity by human natural killer cells. Hum Immunol. 2000;61(8):721–8.
Wilson JL, Charo J, Martin-Fontecha A, Dellabona P, Casorati G, Chambers BJ, et al. NK cell triggering by the human costimulatory molecules CD80 and CD86. J Immunol. 1999;163(8):4207–12.
Costa C, Barber DF, Fodor WL. Human NK cell-mediated cytotoxicity triggered by CD86 and gal alpha 1,3-gal is inhibited in genetically modified porcine cells. J Immunol. 2002;168(8):3808–16.
Galea-Lauri J, Darling D, Gan SU, Krivochtchapov L, Kuiper M, Gaken J, et al. Expression of a variant of CD28 on a subpopulation of human NK cells: implications for B7-mediated stimulation of NK cells. J Immunol. 1999;163(1):62–70.
Kaiser BK, Barahmand-Pour F, Paulsene W, Medley S, Geraghty DE, Strong RK. Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics. J Immunol. 2005;174(5):2878–84.
Braud VM, Allan DS, O'Callaghan CA, Soderstrom K, D'Andrea A, Ogg GS, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998;391(6669):795–9.
Lee N, Llano M, Carretero M, Ishitani A, Navarro F, Lopez-Botet M, et al. HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci U S A. 1998;95(9):5199–204.
Garcia-Beltran WF, Holzemer A, Martrus G, Chung AW, Pacheco Y, Simoneau CR, et al. Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nat Immunol. 2016;17(9):1067–74.
Burian A, Wang KL, Finton KA, Lee N, Ishitani A, Strong RK, et al. HLA-F and MHC-I open conformers bind natural killer cell Ig-like receptor KIR3DS1. PLoS One. 2016;11(9):e0163297.
Kiani Z, Dupuy FP, Bruneau J, Lebouche B, Zhang CX, Jackson E, et al. HLA-F on HLA-null 721.221 cells activates primary NK cells expressing the activating killer Ig-like receptor KIR3DS1. J Immunol. 2018;201(1):113–23.
Isitman G, Lisovsky I, Tremblay-McLean A, Parsons MS, Shoukry NH, Wainberg MA, et al. Natural killer cell education does not affect the magnitude of granzyme B delivery to target cells by antibody-dependent cellular cytotoxicity. AIDS. 2015;29(12):1433–43.
Anfossi N, Andre P, Guia S, Falk CS, Roetynck S, Stewart CA, et al. Human NK cell education by inhibitory receptors for MHC class I. Immunity. 2006;25(2):331–42.
Kim S, Poursine-Laurent J, Truscott SM, Lybarger L, Song YJ, Yang L, et al. Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature. 2005;436(7051):709–13.
Pende D, Rivera P, Marcenaro S, Chang CC, Biassoni R, Conte R, et al. Major histocompatibility complex class I-related chain a and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res. 2002;62(21):6178–86.
Moretta L, Biassoni R, Bottino C, Mingari MC, Moretta A. Human NK-cell receptors. Immunol Today. 2000;21(9):420–2.
Sivori S, Pende D, Bottino C, Marcenaro E, Pessino A, Biassoni R, et al. NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells. Eur J Immunol. 1999;29(5):1656–66.
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;31:227–58.
Chang C, Dietrich J, Harpur AG, Lindquist JA, Haude A, Loke YW, et al. Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. J Immunol. 1999;163(9):4651–4.
Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, et al. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999;285(5428):730–2.
Pende D, Cantoni C, Rivera P, Vitale M, Castriconi R, Marcenaro S, et al. Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin. Eur J Immunol. 2001;31(4):1076–86.
Chen X, Trivedi PP, Ge B, Krzewski K, Strominger JL. Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity. Proc Natl Acad Sci U S A. 2007;104(15):6329–34.
Golden-Mason L, Cox AL, Randall JA, Cheng L, Rosen HR. Increased natural killer cell cytotoxicity and NKp30 expression protects against hepatitis C virus infection in high-risk individuals and inhibits replication in vitro. Hepatology. 2010;52(5):1581–9.
Lo Monaco E, Tremante E, Cerboni C, Melucci E, Sibilio L, Zingoni A, et al. Human leukocyte antigen E contributes to protect tumor cells from lysis by natural killer cells. Neoplasia. 2011;13(9):822–30.
Maier S, Grzeschik M, Weiss EH, Ulbrecht M. Implications of HLA-E allele expression and different HLA-E ligand diversity for the regulation of NK cells. Hum Immunol. 2000;61(11):1059–65.
Lee N, Goodlett DR, Ishitani A, Marquardt H, Geraghty DE. HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. J Immunol. 1998;160(10):4951–60.
Kraemer T, Celik AA, Huyton T, Kunze-Schumacher H, Blasczyk R, Bade-Doding C. HLA-E: presentation of a broader peptide repertoire impacts the cellular immune response-implications on HSCT outcome. Stem Cells Int. 2015;2015:346714.
Celik AA, Kraemer T, Huyton T, Blasczyk R, Bade-Doding C. The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch. Immunogenetics. 2016;68(1):29–41.
Jorgensen PB, Livbjerg AH, Hansen HJ, Petersen T, Hollsberg P. Epstein-Barr virus peptide presented by HLA-E is predominantly recognized by CD8(bright) cells in multiple sclerosis patients. PLoS One. 2012;7(9):e46120.
Romagnani C, Pietra G, Falco M, Millo E, Mazzarino P, Biassoni R, et al. Identification of HLA-E-specific alloreactive T lymphocytes: a cell subset that undergoes preferential expansion in mixed lymphocyte culture and displays a broad cytolytic activity against allogeneic cells. Proc Natl Acad Sci U S A. 2002;99(17):11328–33.
Hammer Q, Ruckert T, Borst EM, Dunst J, Haubner A, Durek P, et al. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells. Nat Immunol. 2018;19(5):453–63.
Goodridge JP, Burian A, Lee N, Geraghty DE. HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. J Immunol. 2013;191(7):3553–62.
Graef T, Moesta AK, Norman PJ, Abi-Rached L, Vago L, Older Aguilar AM, et al. KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C. J Exp Med. 2009;206(11):2557–72.
Boulet S, Sharafi S, Simic N, Bruneau J, Routy JP, Tsoukas CM, et al. Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals. AIDS. 2008;22(5):595–9.
Tallon BJ, Bruneau J, Tsoukas CM, Routy JP, Kiani Z, Tan X, et al. Time to seroconversion in HIV-exposed subjects carrying protective versus non protective KIR3DS1/L1 and HLA-B genotypes. PLoS One. 2014;9(10):e110480.
Norman PJ, bi-Rached L, Gendzekhadze K, Korbel D, Gleimer M, Rowley D, et al. Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nat Genet. 2007;39(9):1092–9.
Yawata M, Yawata N, Draghi M, Little AM, Partheniou F, Parham P. Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. J Exp Med. 2006;203(3):633–45.
Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009;106(42):17858–63.
Yu X, Harden K, C Gonzalez L, Francesco M, Chiang E, Irving B, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48–57.
Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48–57.
Wang F, Hou H, Wu S, Tang Q, Liu W, Huang M, et al. TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals. Eur J Immunol. 2015;45(10):2886–97.
Stanietsky N, Rovis TL, Glasner A, Seidel E, Tsukerman P, Yamin R, et al. Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. Eur J Immunol. 2013;43(8):2138–50.
Liu S, Zhang H, Li M, Hu D, Li C, Ge B, et al. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell Death Differ. 2013;20(3):456–64.
Vales-Gomez M, Reyburn HT, Erskine RA, Lopez-Botet M, Strominger JL. Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94/NKG2-a and the activating receptor CD94/NKG2-C to HLA-E. EMBO J. 1999;18(15):4250–60.
Lisovsky I, Isitman G, Song R, DaFonseca S, Tremblay-McLean A, Lebouche B, et al. A higher frequency of NKG2A+ than of NKG2A− NK cells respond to autologous HIV-infected CD4 cells irrespective of whether they co-express KIR3DL1. J Virol. 2015;89(19):9909–19.