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Structural Immunology pp 1–19Cite as

Structural Basis for Signaling Through Shared Common γ Chain Cytokines

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1172))

Abstract

The common γ chain (γc) family of hematopoietic cytokines consists of six distinct four α-helix bundle soluble ligands that signal through receptors which include the shared γc subunit to coordinate a wide range of physiological processes, in particular, those related to innate and adaptive immune function. Since the first crystallographic structure of a γc family cytokine/receptor signaling complex (the active Interleukin-2 [IL-2] quaternary complex) was determined in 2005 [1], tremendous progress has been made in the structural characterization of this protein family, transforming our understanding of the molecular mechanisms underlying immune activity. Although many conserved features of γc family cytokine complex architecture have emerged, distinguishing details have been observed for individual cytokine complexes that rationalize their unique functional properties. Much work remains to be done in the molecular characterization of γc family signaling, particularly with regard to intracellular activation events, and looking forward, new technologies in structural biophysics will offer further insight into the biology of cytokine signaling to inform the design of targeted therapeutics for treatment of immune-linked diseases such as cancer, infection, and autoimmune disorders.

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References

  1. Wang X, Rickert M, Garcia KC (2005) Structure of the quaternary complex of interleukin-2 with its α, ß, and γc receptors. Science 310:1159–1163

    Article  CAS  PubMed  Google Scholar 

  2. Spangler JB, Moraga I, Mendoza JL, Garcia KC (2015) Insights into cytokine-receptor interactions from cytokine engineering. Annu Rev Immunol 33:139–167. https://doi.org/10.1146/annurev-immunol-032713-120211

    Article  CAS  PubMed  Google Scholar 

  3. Stroud RM, Wells JA (2004) Mechanistic diversity of cytokine receptor signaling across cell membranes. Sci STKE 2004:re7–re7. https://doi.org/10.1126/stke.2312004re7

    Article  Google Scholar 

  4. Wang X, Lupardus P, LaPorte SL, Garcia KC (2009) Structural biology of shared cytokine receptors. Annu Rev Immunol 27:29–60. https://doi.org/10.1146/annurev.immunol.24.021605.090616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Brooks AJ, Dai W, O’Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, Gardon O, Tunny KA, Blucher KM, Morton CJ, Parker MW, Sierecki E, Gambin Y, Gomez GA, Alexandrov K, Wilson IA, Doxastakis M, Mark AE, Waters MJ (2014) Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science 344:1249783. https://doi.org/10.1126/science.1249783

    Article  CAS  PubMed  Google Scholar 

  6. Constantinescu SN, Keren T, Socolovsky M, Nam H, Henis YI, Lodish HF (2001) Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain. Proc Natl Acad Sci USA 98:4379–4384. https://doi.org/10.1073/pnas.081069198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Livnah O, Stura EA, Middleton SA, Johnson DL, Jolliffe LK, Wilson IA (1999) Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. Science 283:987–990

    Article  CAS  PubMed  Google Scholar 

  8. Syed RS, Reid SW, Li C, Cheetham JC, Aoki KH, Liu B, Zhan H, Osslund TD, Chirino AJ, Zhang J, Finer-Moore J, Elliott S, Sitney K, Katz BA, Matthews DJ, Wendoloski JJ, Egrie J, Stroud RM (1998) Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature 395:511–516. https://doi.org/10.1038/26773

    Article  CAS  PubMed  Google Scholar 

  9. Watowich SS, Wu H, Socolovsky M, Klingmuller U, Constantinescu SN, Lodish HF (1996) Cytokine receptor signal transduction and the control of hematopoietic cell development. Annu Rev Cell Dev Biol 12:91–128. https://doi.org/10.1146/annurev.cellbio.12.1.91

    Article  CAS  PubMed  Google Scholar 

  10. Malek TR (2008) The biology of interleukin-2. Annu Rev Immunol 26:453–479. https://doi.org/10.1146/annurev.immunol.26.021607.090357

    Article  CAS  PubMed  Google Scholar 

  11. Murray PJ (2007) The JAK-STAT signaling pathway: input and output integration. J Immunol Balt Md 1950 178:2623–2629

    CAS  Google Scholar 

  12. O’Shea JJ, Plenge R (2012) JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 36:542–550. https://doi.org/10.1016/j.immuni.2012.03.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20. https://doi.org/10.1042/bj20030407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5:375–386. https://doi.org/10.1038/nri1604

    Article  CAS  PubMed  Google Scholar 

  15. Schindler C, Levy DE, Decker T (2007) JAK-STAT signaling: from interferons to cytokines. J Biol Chem 282:20059–20063. https://doi.org/10.1074/jbc.R700016200

    Article  CAS  PubMed  Google Scholar 

  16. van Boxel-Dezaire AHH, Rani MRS, Stark GR (2006) Complex modulation of cell type-specific signaling in response to type I interferons. Immunity 25:361–372. https://doi.org/10.1016/j.immuni.2006.08.014

    Article  CAS  PubMed  Google Scholar 

  17. Overwijk WW, Schluns KS (2009) Functions of γC cytokines in immune homeostasis: current and potential clinical applications. Clin Immunol Orlando Fla 132:153–165. https://doi.org/10.1016/j.clim.2009.03.512

    Article  CAS  Google Scholar 

  18. Rochman Y, Spolski R, Leonard WJ (2009) New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 9:480–490. https://doi.org/10.1038/nri2580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Boyman O, Sprent J (2012) The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 12:180–190. https://doi.org/10.1038/nri3156

    Article  CAS  PubMed  Google Scholar 

  20. Boyman O, Kovar M, Rubinstein MP, Surh CD, Sprent J (2006) Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 311:1924–1927

    Article  CAS  PubMed  Google Scholar 

  21. Granucci F, Vizzardelli C, Pavelka N, Feau S, Persico M, Virzi E, Rescigno M, Moro G, Ricciardi-Castagnoli P (2001) Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat Immunol 2:882

    Article  CAS  PubMed  Google Scholar 

  22. Hershko AY, Suzuki R, Charles N, Alvarez-Errico D, Sargent JL, Laurence A, Rivera J (2011) Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity 35:562–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Setoguchi R, Hori S, Takahashi T, Sakaguchi S (2005) Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 201:723–735. https://doi.org/10.1084/jem.20041982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bachmann MF, Oxenius A (2007) Interleukin 2: from immunostimulation to immunoregulation and back again. EMBO Rep 8:1142–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lenardo MJ (1991) Interleukin-2 programs mouse αβ T lymphocytes for apoptosis. Nature 353:858

    Article  CAS  PubMed  Google Scholar 

  26. Mingari MC, Gerosa F, Carra G, Accolla RS, Moretta A, Zubler RH, Waldmann TA, Moretta L (1984) Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells. Nature 312:641

    Article  CAS  PubMed  Google Scholar 

  27. Pulliam SR, Uzhachenko RV, Adunyah SE, Shanker A (2016) Common gamma chain cytokines in combinatorial immune strategies against cancer. Immunol Lett 169:61–72

    Article  CAS  PubMed  Google Scholar 

  28. Siegel JP, Sharon M, Smith PL, Leonard WJ (1987) The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science 238:75–78

    Article  CAS  PubMed  Google Scholar 

  29. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA (2006) Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci 103:2788–2793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rosenberg SA (2012) Raising the bar: the curative potential of human cancer immunotherapy. Sci Transl Med 4:127ps8. https://doi.org/10.1126/scitranslmed.3003634

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Dhupkar P, Gordon N (2017) Interleukin-2: old and new approaches to enhance immune-therapeutic efficacy. Adv Exp Med Biol 995:33–51. https://doi.org/10.1007/978-3-319-53156-4_2

    Article  CAS  PubMed  Google Scholar 

  32. Krieg C, Létourneau S, Pantaleo G, Boyman O (2010) Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci 107:11906–11911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K (1992) Cloning of the gamma chain of the human IL-2 receptor. Science 257:379–382

    Article  CAS  PubMed  Google Scholar 

  34. Nelson BH, Willerford DM (1998) Biology of the interleukin-2 receptor. In: Advances in immunology. Elsevier, pp 1–81

    Google Scholar 

  35. Liao W, Lin J-X, Leonard WJ (2013) Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38:13–25. https://doi.org/10.1016/j.immuni.2013.01.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Carson WE, Fehniger TA, Haldar S, Eckhert K, Lindemann MJ, Lai C-F, Croce CM, Baumann H, Caligiuri MA (1997) A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest 99:937–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Waldmann TA, Dubois S, Tagaya Y (2001) Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14:105–110

    CAS  PubMed  Google Scholar 

  38. Zhang X, Sun S, Hwang I, Tough DF, Sprent J (1998) Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8:591–599

    Article  CAS  PubMed  Google Scholar 

  39. Bazan JF, McKay DB (1992) Unraveling the structure of IL-2. Science 257:410–413

    Article  CAS  PubMed  Google Scholar 

  40. Smith KA (1993) Lowest dose interleukin-2 immunotherapy. BLOOD-NY 81:1414–1414

    Article  CAS  Google Scholar 

  41. Wilson CGM, Arkin MR (2010) Small-molecule inhibitors of IL-2/IL-2R: lessons learned and applied. In: Small-Molecule inhibitors of protein-protein interactions. Springer, pp 25–59

    Google Scholar 

  42. Teshigawara K, Wang H-M, Kato K, Smith KA (1987) Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med 165:223–238

    Article  CAS  PubMed  Google Scholar 

  43. Arima N, Kamio M, Imada K, Hori T, Hattori T, Tsudo M, Okuma M, Uchiyama T (1992) Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling. J Exp Med 176:1265–1272

    Article  CAS  PubMed  Google Scholar 

  44. Sana TR, Wu Z, Smith KA, Ciardelli TL (1994) Expression and ligand binding characterization of the beta-subunit (p75) ectodomain of the interleukin-2 receptor. Biochemistry 33:5838–5845

    Article  CAS  PubMed  Google Scholar 

  45. Wu Z, Goldstein B, Laue TM, Liparoto SF, Nemeth MJ, Ciardelli TL (1999) Solution assembly of the pseudo-high affinity and intermediate affinity interleukin-2 receptor complexes. Protein Sci 8:482–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Johnson K, Choi Y, Wu Z, Ciardelli T, Granzow R, Whalen C, Sana T, Pardee G, Smith K, Creasey A (1994) Soluble IL-2 receptor beta and gamma subunits: ligand binding and cooperativity. Eur Cytokine Netw 5:23–34

    CAS  PubMed  Google Scholar 

  47. Wang H-M, Smith KA (1987) The interleukin 2 receptor. Functional consequences of its bimolecular structure. J Exp Med 166:1055–1069

    Article  CAS  PubMed  Google Scholar 

  48. Waldmann TA (2006) The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 6:595

    Article  CAS  PubMed  Google Scholar 

  49. Waldmann TA, Dubois S, Müller J, Goldman C, Damjanovich S (2005) Transmembrane signals mediated by IL-2 and IL-15 control the life and death of lymphocytes. In: Biophysical aspects of transmembrane signaling. Springer, pp 97–121

    Google Scholar 

  50. Fehniger TA, Cooper MA, Caligiuri MA (2002) Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev 13:169–183

    Article  CAS  PubMed  Google Scholar 

  51. Ring AM, Lin J-X, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Özkan E, Leonard WJ, Garcia KC (2012) Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat Immunol 13:1187–1195. https://doi.org/10.1038/ni.2449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Loro E, Ramaswamy G, Chandra A, Tseng W-J, Mishra MK, Shore EM, Khurana TS (2017) IL15RA is required for osteoblast function and bone mineralization. Bone 103:20–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O (2007) Crystal structure of the interleukin-15· interleukin-15 receptor α complex insights into TRANS and CIS presentation. J Biol Chem 282:37191–37204

    Article  CAS  PubMed  Google Scholar 

  54. Stoklasek TA, Schluns KS, Lefrançois L (2006) Combined IL-15/IL-15Rα immunotherapy maximizes IL-15 activity in vivo. J Immunol 177:6072–6080

    Article  CAS  PubMed  Google Scholar 

  55. Mortier E, Quéméner A, Vusio P, Lorenzen I, Boublik Y, Grotzinger J, Plet A, Jacques Y (2005) Soluble IL-15Rα sushi as a selective and potent agonist of IL-15 action through IL-15Rβ/γ: hyper-agonist IL-15-IL-15Rα fusion proteins. J Biol Chem

    Google Scholar 

  56. Hu Q, Ye X, Qu X, Cui D, Zhang L, Xu Z, Wan H, Zhang L, Tao W (2018) Discovery of a novel IL-15 based protein with improved developability and efficacy for cancer immunotherapy. Sci Rep 8:7675. https://doi.org/10.1038/s41598-018-25987-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Van den Bergh JM, Van Tendeloo VF, Smits EL (2015) Interleukin-15: new kid on the block for antitumor combination therapy. Cytokine Growth Factor Rev 26:15–24

    Article  PubMed  CAS  Google Scholar 

  58. Bessard A, Solé V, Bouchaud G, Quéméner A, Jacques Y (2009) High antitumor activity of RLI, an interleukin-15 (IL-15)–IL-15 receptor α fusion protein, in metastatic melanoma and colorectal cancer. Mol Cancer Ther 8:2736–2745. https://doi.org/10.1158/1535-7163.MCT-09-0275

    Article  CAS  PubMed  Google Scholar 

  59. Chen S, Huang Q, Liu J, Xing J, Zhang N, Liu Y, Wang Z, Li Q (2015) A targeted IL-15 fusion protein with potent anti-tumor activity. Cancer Biol Ther 16:1415–1421. https://doi.org/10.1080/15384047.2015.1071739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yang X, Kallarakal A, Saptharishi N, Jiang H, Yang Z, Xie Y, Mitra G, Zheng XX, Strom TB, Soman G (2013) Molecular characterization and functional activity of an IL-15 antagonist MutIL-15/Fc human fusion protein. Mol Pharm 10:717–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ma A, Koka R, Burkett P (2006) Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 24:657–679

    Article  CAS  PubMed  Google Scholar 

  62. Collins L, Tsien WH, Seals C, Hakimi J, Weber D, Bailon P, Hoskings J, Greene WC, Toome V, Ju G (1988) Identification of specific residues of human interleukin 2 that affect binding to the 70-kDa subunit (p70) of the interleukin 2 receptor. Proc Natl Acad Sci 85:7709–7713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Eisenman J, Ahdieh M, Beers C, Brasel K, Kennedy MK, Le T, Bonnert TP, Paxton RJ, Park LS (2002) Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity. Cytokine 20:121–129

    Article  CAS  PubMed  Google Scholar 

  64. Zurawski SM, Vega F Jr, Doyle EL, Huyghe B, Flaherty K, McKay DB, Zurawski G (1993) Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor. EMBO J 12:5113–5119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Swain SL, Weinberg AD, English M, Huston G (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol 145:3796–3806

    CAS  PubMed  Google Scholar 

  66. Hage T, Sebald W, Reinemer P (1999) Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface. Cell 97:271–281

    Article  CAS  PubMed  Google Scholar 

  67. Wynn TA (2015) Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol 15:271–282. https://doi.org/10.1038/nri3831

    Article  CAS  PubMed  Google Scholar 

  68. Junttila IS, Creusot RJ, Moraga I, Bates DL, Wong MT, Alonso MN, Suhoski MM, Lupardus P, Meier-Schellersheim M, Engleman EG, Utz PJ, Fathman CG, Paul WE, Garcia KC (2012) Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines. Nat Chem Biol 8:990–998. https://doi.org/10.1038/nchembio.1096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC (2008) Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell 132:259–272. https://doi.org/10.1016/j.cell.2007.12.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Murata T, Taguchi J, Puri RK (1998) Interleukin-13 receptor α′ but not α chain: a functional component of interleukin-4 receptors. Blood 91(10):3884–3891

    Article  CAS  PubMed  Google Scholar 

  71. Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17:701–738. https://doi.org/10.1146/annurev.immunol.17.1.701

    Article  CAS  PubMed  Google Scholar 

  72. Hage T, Reinemer P, Sebald W (1998) Crystals of a 1:1 complex between human interleukin-4 and the extracellular domain of its receptor alpha chain. Eur J Biochem 258:831–836

    Article  CAS  PubMed  Google Scholar 

  73. Letzelter F, Wang Y, Sebald W (1998) The interleukin-4 site-2 epitope determining binding of the common receptor gamma chain. Eur J Biochem 257:11–20

    Article  CAS  PubMed  Google Scholar 

  74. Grunewald SM, Kunzmann S, Schnarr B, Ezernieks J, Sebald W, Duschl A (1997) A murine interleukin-4 antagonistic mutant protein completely inhibits interleukin-4-induced cell proliferation, differentiation, and signal transduction. J Biol Chem 272:1480–1483. https://doi.org/10.1074/jbc.272.3.1480

    Article  CAS  PubMed  Google Scholar 

  75. Wang Y, Shen B-J, Sebald W (1997) A mixed-charge pair in human interleukin 4 dominates high-affinity interaction with the receptor chain. Proc Natl Acad Sci 94:1657–1662. https://doi.org/10.1073/pnas.94.5.1657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Mazzucchelli R, Durum SK (2007) Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol 7:144–154. https://doi.org/10.1038/nri2023

    Article  CAS  PubMed  Google Scholar 

  77. Goldrath AW, Sivakumar PV, Glaccum M, Kennedy MK, Bevan MJ, Benoist C, Mathis D, Butz EA (2002) Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med 195:1515–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Schluns KS, Kieper WC, Jameson SC, Lefrançois L (2000) Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat Immunol 1:426–432. https://doi.org/10.1038/80868

    Article  CAS  PubMed  Google Scholar 

  79. Benbernou N, Muegge K, Durum SK (2000) Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Rα. J Biol Chem 275(10):7060–7065

    Article  CAS  PubMed  Google Scholar 

  80. Dadi H, Ke S, Roifman CM (1994) Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor is dependent on protein tyrosine kinase activity. Blood 84:1579–1586

    Article  CAS  PubMed  Google Scholar 

  81. Page TH, Lali FV, Foxwell BM (1995) Interleukin-7 activates p56lck and p59fyn, two tyrosine kinases associated with the p90 interleukin-7 receptor in primary human T cells. Eur J Immunol 25:2956–2960. https://doi.org/10.1002/eji.1830251036

    Article  CAS  PubMed  Google Scholar 

  82. Seckinger P, Fougereau M (1994) Activation of SRC family kinases in human pre-B cells by IL-7. J Immunol Baltim Md 1950 153:97–109

    CAS  Google Scholar 

  83. Al-Shami A, Spolski R, Kelly J, Fry T, Schwartzberg PL, Pandey A, Mackall CL, Leonard WJ (2004) A role for thymic stromal lymphopoietin in CD4(+) T cell development. J Exp Med 200:159–168. https://doi.org/10.1084/jem.20031975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Rocha B, Dautigny N, Pereira P (1989) Peripheral T lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo. Eur J Immunol 19:905–911. https://doi.org/10.1002/eji.1830190518

    Article  CAS  PubMed  Google Scholar 

  85. McElroy CA, Dohm JA (1993) Walsh STR (2009) Structural and biophysical studies of the human IL-7/IL-7Ralpha complex. Struct Lond Engl 17:54–65. https://doi.org/10.1016/j.str.2008.10.019

    Article  CAS  Google Scholar 

  86. Walsh STR (2012) Structural insights into the common γ-chain family of cytokines and receptors from the interleukin-7 pathway. Immunol Rev 250:303–316. https://doi.org/10.1111/j.1600-065X.2012.01160.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. McElroy CA, Holland PJ, Zhao P, Lim J-M, Wells L, Eisenstein E, Walsh STR (2012) Structural reorganization of the interleukin-7 signaling complex. Proc Natl Acad Sci USA 109:2503–2508. https://doi.org/10.1073/pnas.1116582109

    Article  PubMed  PubMed Central  Google Scholar 

  88. Verstraete K, van Schie L, Vyncke L, Bloch Y, Tavernier J, Pauwels E, Peelman F, Savvides SN (2014) Structural basis of the proinflammatory signaling complex mediated by TSLP. Nat Struct Mol Biol 21:375–382. https://doi.org/10.1038/nsmb.2794

    Article  CAS  PubMed  Google Scholar 

  89. Shen BJ, Hage T, Sebald W (1996) Global and local determinants for the kinetics of interleukin-4/interleukin-4 receptor alpha chain interaction. A biosensor study employing recombinant interleukin-4-binding protein. Eur J Biochem 240:252–261

    Article  CAS  PubMed  Google Scholar 

  90. Elyaman W, Bradshaw EM, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, Bettelli E, Oukka M, van Snick J, Renauld J-C, Kuchroo VK, Khoury SJ (2009) IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci 106:12885–12890. https://doi.org/10.1073/pnas.0812530106

    Article  PubMed  PubMed Central  Google Scholar 

  91. Goswami R, Kaplan MH (2011) A brief history of IL-9. J Immunol 186:3283–3288. https://doi.org/10.4049/jimmunol.1003049

    Article  CAS  PubMed  Google Scholar 

  92. Kaplan MH (2013) Th9 cells: differentiation and disease. Immunol Rev 252:104–115. https://doi.org/10.1111/imr.12028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Li H, Rostami A (2010) IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity. J Neuroimmune Pharmacol 5:198–209. https://doi.org/10.1007/s11481-009-9186-y

    Article  PubMed  Google Scholar 

  94. Spolski R, Leonard WJ (2010) IL-21 and T follicular helper cells. Int Immunol 22:7–12. https://doi.org/10.1093/intimm/dxp112

    Article  CAS  PubMed  Google Scholar 

  95. Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, Oukka M, Kuchroo VK (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448:484–487. https://doi.org/10.1038/nature05970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C (2008) A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 29:127–137. https://doi.org/10.1016/j.immuni.2008.06.001

    Article  CAS  PubMed  Google Scholar 

  97. Zeng R, Spolski R, Finkelstein SE, Oh S, Kovanen PE, Hinrichs CS, Pise-Masison CA, Radonovich MF, Brady JN, Restifo NP, Berzofsky JA, Leonard WJ (2005) Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J Exp Med 201:139–148. https://doi.org/10.1084/jem.20041057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ozaki K, Leonard WJ (2002) Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem 277:29355–29358. https://doi.org/10.1074/jbc.R200003200

    Article  CAS  PubMed  Google Scholar 

  99. Elsaesser H, Sauer K, Brooks DG (2009) IL-21 is required to control chronic viral infection. Science 324:1569–1572. https://doi.org/10.1126/science.1174182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Fröhlich A, Kisielow J, Schmitz I, Freigang S, Shamshiev AT, Weber J, Marsland BJ, Oxenius A, Kopf M (2009) IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 324:1576–1580. https://doi.org/10.1126/science.1172815

    Article  CAS  PubMed  Google Scholar 

  101. Hashmi MH, Van Veldhuizen PJ (2010) Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin’s lymphoma. Expert Opin Biol Ther 10:807–817. https://doi.org/10.1517/14712598.2010.480971

    Article  CAS  PubMed  Google Scholar 

  102. Yi JS, Du M, Zajac AJ (2009) A vital role for interleukin-21 in the control of a chronic viral infection. Science 324:1572–1576. https://doi.org/10.1126/science.1175194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zeng R, Spolski R, Casas E, Zhu W, Levy DE, Leonard WJ (2007) The molecular basis of IL-21–mediated proliferation. Blood 109:4135–4142. https://doi.org/10.1182/blood-2006-10-054973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ (2000) Cloning of a type I cytokine receptor most related to the IL-2 receptor β chain. Proc Natl Acad Sci 97:11439–11444. https://doi.org/10.1073/pnas.200360997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D (2000) Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 408:57–63. https://doi.org/10.1038/35040504

    Article  CAS  PubMed  Google Scholar 

  106. Pellegrini M, Mak TW, Ohashi PS (2010) Fighting cancers from within: augmenting tumor immunity with cytokine therapy. Trends Pharmacol Sci 31:356–363. https://doi.org/10.1016/j.tips.2010.05.003

    Article  CAS  PubMed  Google Scholar 

  107. Hamming OJ, Kang L, Svensson A, Karlsen JL, Rahbek-Nielsen H, Paludan SR, Hjorth SA, Bondensgaard K, Hartmann R (2012) Crystal structure of interleukin-21 receptor (IL-21R) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R. J Biol Chem 287:9454–9460. https://doi.org/10.1074/jbc.M111.311084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhang J-L, Foster D, Sebald W (2003) Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma-chain. Biochem Biophys Res Commun 300:291–296

    Article  CAS  PubMed  Google Scholar 

  109. Furmanek A, Hofsteenge J (2000) Protein C-mannosylation: facts and questions. Acta Biochim Pol 47:781–789

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA

    Huilin Yang & Jamie B. Spangler

  2. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Rakeeb Kureshi & Jamie B. Spangler

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  1. Huilin Yang
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  2. Rakeeb Kureshi
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  3. Jamie B. Spangler
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Correspondence to Jamie B. Spangler .

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  1. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China

    Tengchuan Jin

  2. Department of Biological Science, Florida State University, Tallahassee, FL, USA

    Qian Yin

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Yang, H., Kureshi, R., Spangler, J.B. (2019). Structural Basis for Signaling Through Shared Common γ Chain Cytokines. In: Jin, T., Yin, Q. (eds) Structural Immunology. Advances in Experimental Medicine and Biology, vol 1172. Springer, Singapore. https://doi.org/10.1007/978-981-13-9367-9_1

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