Targeting the binding interface on a shared receptor subunit of a cytokine family enables the inhibition of multiple member cytokines with selectable target spectrum

Journal of Biological Chemistry

Volumn 290, Issue 37, 2015, Pages 22338-22351

  Nata, Toshie ^a   Basheer, Asjad ^b   Cocchi, Fiorenza ^a   Van Besien, Richard ^a   Massoud, Raya ^c   Jacobson, Steven ^c   Azimi, Nazli ^b   Tagaya, Yutaka ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b Bioniz   (United States)

^c NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DISEASE CONTROL; MOLECULES; MONOCLONAL ANTIBODIES; PEPTIDES;

BINDING INTERFACE; MALIGNANT DISEASE; MUTATIONAL ANALYSIS; NEUTRALIZING ANTIBODIES; SIGNALING RECEPTOR; STRUCTURAL ASPECTS; THERAPEUTIC INTERVENTION; THERAPEUTIC STRATEGY;

ANTIBODIES;

BNZ132 1; INTERLEUKIN 13; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR GAMMA; INTERLEUKIN 21; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 7; INTERLEUKIN 9; MACROGOL; PEPTIDE; UNCLASSIFIED DRUG; CYTOKINE; IL2RG PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; IN VIVO STUDY; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS INHIBITION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; TRANSLATION INITIATION; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHEMISTRY; GENETICS; MALE; METABOLISM;

CELLS, CULTURED; CYTOKINES; FEMALE; HUMANS; INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT; MALE; PEPTIDES;

EID: 84941584635     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.661074     Document Type: Article

References (68)

1. Bazan, J. F. (1992) Unraveling the structure of IL-2. Science 257, 410-413
2. Ozaki, K., and Leonard, W. J. (2002) Cytokine and cytokine receptor pleiotropy and redundancy. J. Biol. Chem. 277, 29355-29358
3. Rochman, Y., Spolski, R., and Leonard, W. J. (2009) New insights into the regulation of T cells by γ (c) family cytokines. Nat. Rev. Immunol. 9, 480-490
4. Macchi, P., Villa, A., Giliani, S., Sacco, M. G., Frattini, A., Porta, F., Ugazio, A. G., Johnston, J. A., Candotti, F., and O'Shea, J. J. (1995) Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 377, 65-68
5. Noguchi, M., Yi, H., Rosenblatt, H. M., Filipovich, A. H., Adelstein, S., Modi, W. S., McBride, O. W., and Leonard, W. J. (1993) IL-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73, 147-157
6. Russell, S. M., Tayebi, N., Nakajima, H., Riedy, M. C., Roberts, J. L., Aman, M. J., Migone, T. S., Noguchi, M., Markert, M. L., Buckley, R. H., O'Shea, J. J., and Leonard, W. J. (1995) Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science 270, 797-800
7. Nosaka, T., van Deursen, J. M., Tripp, R. A., Thierfelder, W. E., Witthuhn, B. A., McMickle, A. P., Doherty, P. C., Grosveld, G. C., and Ihle, J. N. (1995) Defective lymphoid development in mice lacking Jak3. Science 270, 800-802
8. Malek, T. R., Yu, A., Vincek, V., Scibelli, P., and Kong, L. (2002) CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rβ-deficient mice. Implications for the nonredundant function of IL-2. Immunity 17, 167-178
9. Glas, J., Stallhofer, J., Ripke, S., Wetzke, M., Pfennig, S., Klein, W., Epplen, J. T., Griga, T., Schiemann, U., Lacher, M., Koletzko, S., Folwaczny, M., Lohse, P., Göke, B., Ochsenkühn, T., et al. (2009) Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease. Am. J. Gastroenterol. 104, 1737-1744
10. Festen, E. A., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefèbvre, C., Brant, S. R., Cho, J. H., Silverberg, M. S., Taylor, K. D., de Jong, D. J., Stokkers, P. C., Mcgovern, D., Palmieri, O., et al. (2009) Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis. Gut 58, 799-804
11. Márquez, A., Orozco, G., Martínez, A., Palomino-Morales, R., Fernández-Arquero, M., Mendoza, J. L., Taxonera, C., Díaz-Rubio, M., Gómez-García, M., Nieto, A., López-Nevot, M. A., de la Concha, E. G., Martín, J., and Urcelay, E. (2009) Novel association of the IL2-IL21 region with inflammatory bowel disease. Am. J. Gastroenterol. 104, 1968-1975
12. Steinke, J. W., Borish, L., and Rosenwasser, L. J. (2003) 5. Genetics of hypersensitivity. J. Allergy Clin. Immunol. 111, S495-S501
13. Lundström, W., Fewkes, N. M., and Mackall, C. L. (2012) IL-7 in human health and disease. Semin. Immunol. 24, 218-224
14. Shimbara, A., Christodoulopoulos, P., Soussi-Gounni, A., Olivenstein, R., Nakamura, Y., Levitt, R. C., Nicolaides, N. C., Holroyd, K. J., Tsicopoulos, A., Lafitte, J. J., Wallaert, B., and Hamid, Q. A. (2000) IL-9 and its receptor in allergic and nonallergic lung disease: increased expression in asthma. J. Allergy Clin. Immunol. 105, 108-115
15. Nicolaides, N. C., Holroyd, K. J., Ewart, S. L., Eleff, S. M., Kiser, M. B., Dragwa, C. R., Sullivan, C. D., Grasso, L., Zhang, L. Y., Messler, C. J., Zhou, T., Kleeberger, S. R., Buetow, K. H., and Levitt, R. C. (1997) IL9: a candidate gene for asthma. Proc. Natl. Acad. Sci. U. S. A. 94, 13175-13180
16. Fehniger, T. A., Suzuki, K., Ponnappan, A., Van Deusen, J. B., Cooper, M. A., Florea, S. M., Freud, A. G., Robinson, M. L., Durbin, J., and Caligiuri, M. A. (2001) Fatal leukemia in IL15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. J. Exp. Med. 193, 219-231
17. Sato, N., Sabzevari, H., Fu, S., Ju, W., Petrus, M. N., Bamford, R. N., Waldmann, T. A., and Tagaya, Y. (2011) Development of an IL-15-autocrine CD8 T-cell leukemia in IL-15-transgenic mice requires the cis expression of IL-15Rα. Blood 117, 4032-4040
18. Zambello, R., Facco, M., Trentin, L., Sancetta, R., Tassinari, C., Perin, A., Milani, A., Pizzolo, G., Rodeghiero, F., Agostini, C., Meazza, R., Ferrini, S., and Semenzato, G. (1997) IL-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes. Blood 89, 201-211
19. Meresse, B., Chen, Z., Ciszewski, C., Tretiakova, M., Bhagat, G., Krausz, T. N., Raulet, D. H., Lanier, L. L., Groh, V., Spies, T., Ebert, E. C., Green, P. H., and Jabri, B. (2004) Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357-366
20. Tang, F., Chen, Z., Ciszewski, C., Setty, M., Solus, J., Tretiakova, M., Ebert, E., Han, J., Lin, A., Guandalini, S., Groh, V., Spies, T., Green, P., and Jabri, B. (2009) Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15. J. Exp. Med. 206, 707-719
21. Meresse, B., Curran, S. A., Ciszewski, C., Orbelyan, G., Setty, M., Bhagat, G., Lee, L., Tretiakova, M., Semrad, C., Kistner, E., Winchester, R. J., Braud, V., Lanier, L. L., Geraghty, D. E., Green, P. H., et al. (2006) Reprogramming of CTLs into natural killer-like cells in celiac disease. J. Exp. Med. 203, 1343-1355
22. Jabri, B., de Serre, N. P., Cellier, C., Evans, K., Gache, C., Carvalho, C., Mougenot, J. F., Allez, M., Jian, R., Desreumaux, P., Colombel, J. F., Matuchansky, C., Cugnenc, H., Lopez-Botet, M., Vivier, E., et al. (2000) Selective expansion of intraepithelial lymphocytes expressing the HLA-Especific natural killer receptor CD94 in celiac disease. Gastroenterology 118, 867-879
23. Bhagat, G., Naiyer, A. J., Shah, J. G., Harper, J., Jabri, B., Wang, T. C., Green, P. H., and Manavalan, J. S. (2008) Small intestinal CD86+TCRγγ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease. J. Clin. Invest. 118, 281-293
24. Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D. A., Jabri, B., and Chang, E. B. (2012) Dietaryfatinduced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487, 104-108
25. Yokoyama, S., Perera, P. Y., Waldmann, T. A., Hiroi, T., and Perera, L. P. (2013) Tofacitinib, a Janus kinase inhibitor demonstrates efficacy in an IL-15 transgenic mouse model that recapitulates pathologic manifestations of celiac disease. J. Clin. Immunol. 33, 586-594
26. Bodd, M., Ráki, M., Tollefsen, S., Fallang, L. E., Bergseng, E., Lundin, K. E., and Sollid, L. M. (2010) HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol. 3, 594-601
27. Leonard, W. J., and Spolski, R. (2005) IL-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat. Rev. Immunol. 5, 688-698
28. Chtanova, T., Tangye, S. G., Newton, R., Frank, N., Hodge, M. R., Rolph, M. S., and Mackay, C. R. (2004) T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J. Immunol. 173, 68-78
29. Amadi-Obi, A., Yu, C. R., Liu, X., Mahdi, R. M., Clarke, G. L., Nussenblatt, R. B., Gery, I., Lee, Y. S., and Egwuagu, C. E. (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat. Med. 13, 711-718
30. Costanzo, A., Chimenti, M. S., Botti, E., Caruso, R., Sarra, M., and Monteleone, G. (2010) IL-21 in the pathogenesis and treatment of skin diseases. J. Dermatol. Sci. 60, 61-66
31. Sarra, M., Pallone, F., and Monteleone, G. (2013) IL-21 in chronic inflammatory diseases. BioFactors 39, 368-373
32. Changelian, P. S., Flanagan, M. E., Ball, D. J., Kent, C. R., Magnuson, K. S., Martin, W. H., Rizzuti, B. J., Sawyer, P. S., Perry, B. D., Brissette, W. H., McCurdy, S. P., Kudlacz, E. M., Conklyn, M. J., Elliott, E. A., Koslov, E. R., et al. (2003) Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302, 875-878
33. Tagaya, Y., Burton, J. D., Miyamoto, Y., and Waldmann, T. A. (1996) Identification of a novel receptor/signal transduction pathway for IL-15/T in mast cells. EMBO J. 15, 4928-4939
34. Antal, Z., Baker, J. C., Smith, C., Jarchum, I., Babad, J., Mukherjee, G., Yang, Y., Sidney, J., Sette, A., Santamaria, P., and Di Lorenzo, T. P. (2012) Beyond HLA-A∗0201: new HLA-transgenic nonobese diabetic mouse models of type 1 diabetes identify the insulin C-peptide as a rich source of CD8+ T cell epitopes. J. Immunol. 188, 5766-5775
35. Notredame, C., Higgins, D. G., and Heringa, J. (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205-217
36. Ju, W., Zhang, M., Jiang, J. K., Thomas, C. J., Oh, U., Bryant, B. R., Chen, J., Sato, N., Tagaya, Y., Morris, J. C., Janik, J. E., Jacobson, S., and Waldmann, T. A. (2011) CP-690, 550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP. Blood 117, 1938-1946
37. Wang, X., Rickert, M., and Garcia, K. C. (2005) Structure of the quaternary complex of IL-2 with its α, β, and γc receptors. Science 310, 1159-1163
38. Ring, A. M., Lin, J. X., Feng, D., Mitra, S., Rickert, M., Bowman, G. R., Pande, V. S., Li, P., Moraga, I., Spolski, R., Ozkan, E., Leonard, W. J., and Garcia, K. C. (2012) Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat. Immunol. 13, 1187-1195
39. Bamford, R. N., Grant, A. J., Burton, J. D., Peters, C., Kurys, G., Goldman, C. K., Brennan, J., Roessler, E., and Waldmann, T. A. (1994) The interleukin (IL) 2 receptor β chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc. Natl. Acad. Sci. U. S. A. 91, 4940-4944
40. Grabstein, K. H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C., Richardson, J., Schoenborn, M. A., and Ahdieh, M. (1994) Cloning of a T cell growth factor that interacts with the β chain of the IL-2 receptor. Science 264, 965-968
41. Vanderhoek, J. Y., Tare, N. S., Bailey, J. M., Goldstein, A. L., and Pluznik, D. H. (1982) New role for 15-hydroxyeicosatetraenoic acid. Activator of leukotriene biosynthesis in PT-18 mast/basophil cells. J. Biol. Chem. 257, 12191-12195
42. Boulay, J. L., O'Shea, J. J., and Paul, W. E. (2003) Molecular phylogeny within type I cytokines and their cognate receptors. Immunity 19, 159-163
43. Cheng, Y., and Prusoff, W. H. (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108
44. Craig, D. A. (1993) The Cheng-Prusoff relationship: something lost in the translation. Trends Pharmacol. Sci. 14, 89-91
45. Tendler, C. L., Greenberg, S. J., Blattner, W. A., Manns, A., Murphy, E., Fleisher, T., Hanchard, B., Morgan, O., Burton, J. D., and Nelson, D. L. (1990) Transactivation of IL2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy. Proc. Natl. Acad. Sci. U. S. A. 87, 5218-5222
46. Azimi, N., Jacobson, S., Leist, T., and Waldmann, T. A. (1999) Involvement of IL-15 in the pathogenesis of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: implications for therapy with a monoclonal antibody directed to the IL-2/15R β receptor. J. Immunol. 163, 4064-4072
47. Chen, J., Petrus, M., Bryant, B. R., Phuc Nguyen, V., Stamer, M., Goldman, C. K., Bamford, R., Morris, J. C., Janik, J. E., and Waldmann, T. A. (2008) Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism. Blood 111, 5163-5172
48. Morrison, K. L., and Weiss, G. A. (2001) Combinatorial alanine-scanning. Curr. Opin. Chem. Biol. 5, 302-307
49. Antony, P. A., Paulos, C. M., Ahmadzadeh, M., Akpinarli, A., Palmer, D. C., Sato, N., Kaiser, A., Hinrichs, C. S., Heinrichs, C., Klebanoff, C. A., Tagaya, Y., and Restifo, N. P. (2006) IL-2-dependent mechanisms of tolerance and immunity in vivo. J. Immunol. 176, 5255-5266
50. Boyman, O., Krieg, C., Letourneau, S., Webster, K., Surh, C. D., and Sprent, J. (2012) Selectively expanding subsets of T cells in mice by injection of interleukin-2/antibody complexes: implications for transplantation tolerance. Transplant. Proc. 44, 1032-1034
51. Marks-Konczalik, J., Dubois, S., Losi, J. M., Sabzevari, H., Yamada, N., Feigenbaum, L., Waldmann, T. A., and Tagaya, Y. (2000) IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 97, 11445-11450
52. Matsuura, E., Yamano, Y., and Jacobson, S. (2010) Neuroimmunity of HTLV-I infection. J. Neuroimmune Pharmacol. 5, 310-325
53. Liao, W., Lin, J. X., and Leonard, W. J. (2013) IL-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38, 13-25
54. La Porte, S. L., Juo, Z. S., Vaclavikova, J., Colf, L. A., Qi, X., Heller, N. M., Keegan, A. D., and Garcia, K. C. (2008) Molecular and structural basis of cytokine receptor pleiotropy in the IL-4/13 system. Cell 132, 259-272
55. Oh, C. K., Raible, D., Geba, G. P., and Molfino, N. A. (2011) Biology of the IL-9 pathway and its therapeutic potential for the treatment of asthma. Inflamm. Allergy Drug Targets 10, 180-186
56. Steinke, J. W. (2010) Current prospective of anti-IL-4, -IL-9, and -IL-13 therapies in allergic disease. Recent Pat. Inflamm. Allergy Drug Discov. 4, 222-230
57. West, K. (2009) CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders. Curr. Opin. Investig. Drugs 10, 491-504
58. Jiang, J. K., Ghoreschi, K., Deflorian, F., Chen, Z., Perreira, M., Pesu, M., Smith, J., Nguyen, D. T., Liu, E. H., Leister, W., Costanzi, S., O'Shea, J. J., and Thomas, C. J. (2008) Examining the chirality, conformation and selective kinase inhibition of 3-((3R, 4R)-4-methyl-3-(methyl (7Hpyrrolo[2, 3-d]pyrimidin-4-yl) amino) piperidin-1-y l)-3-oxopropanenitrile (CP-690, 550). J. Med. Chem. 51, 8012-8018
59. Garber, K. (2011) Pfizer's JAK inhibitor sails through phase 3 in rheumatoid arthritis. Nat. Biotechnol. 29, 467-468
60. Azimi, N., Nagai, M., Jacobson, S., and Waldmann, T. A. (2001) IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients. Proc. Natl. Acad. Sci. U. S. A. 98, 14559-14564
61. Nowak, E. C., Weaver, C. T., Turner, H., Begum-Haque, S., Becher, B., Schreiner, B., Coyle, A. J., Kasper, L. H., and Noelle, R. J. (2009) IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med. 206, 1653-1660
62. Li, H., Nourbakhsh, B., Ciric, B., Zhang, G. X., and Rostami, A. (2010) Neutralization of IL-9 ameliorates experimental autoimmune encephalomyelitis by decreasing the effector T cell population. J. Immunol. 185, 4095-4100
63. Saikali, P., Antel, J. P., Pittet, C. L., Newcombe, J., and Arbour, N. (2010) Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis. J. Immunol. 185, 5693-5703
64. McInnes, I. B., and Liew, F. Y. (2005) Cytokine networks-towards new therapies for rheumatoid arthritis. Nat. Clin. Pract. Rheumatol. 1, 31-39
65. Hartgring, S. A., Bijlsma, J. W., Lafeber, F. P., and van Roon, J. A. (2006) Interleukin-7 induced immunopathology in arthritis. Ann. Rheum. Dis. 65, Suppl. 3, 69-74
66. Kishimoto, T. (2010) IL-6: from its discovery to clinical applications. Int. Immunol. 22, 347-352
67. Young, D. A., Hegen, M., Ma, H. L., Whitters, M. J., Albert, L. M., Lowe, L., Senices, M., Wu, P. W., Sibley, B., Leathurby, Y., Brown, T. P., Nickerson-Nutter, C., Keith, J. C., Jr., and Collins, M. (2007) Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum. 56, 1152-1163
68. Tagaya, Y., and Azimi, N. (June 4, 2013) U. S. Patent 08455449