1932

Abstract

Over the past 15 years, investigators have shown that T lymphocytes can recognize not only peptides in the context of MHC class I and class II molecules but also foreign and self-lipids in association with the nonclassical MHC class I–like molecules, CD1 proteins. In this review, we describe the most recent events in the field, with particular emphasis on () structural and functional aspects of lipid presentation by CD1 molecules, () the development of CD1d-restricted invariant natural killer T (iNKT) cells and transcription factors required for their differentiation, () the ability of iNKT cells to modulate innate and adaptive immune responses through their cross talk with lymphoid and myeloid cells, and () MR1-restricted and group I (CD1a, CD1b, and CD1c)–restricted T cells.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-032713-120243
2014-03-21
2024-06-14
Loading full text...

Full text loading...

/deliver/fulltext/immunol/32/1/annurev-immunol-032713-120243.html?itemId=/content/journals/10.1146/annurev-immunol-032713-120243&mimeType=html&fmt=ahah

Literature Cited

  1. Dellabona P, Casorati G, Friedli B, Angman L, Sallusto F. 1.  et al. 1993. In vivo persistence of expanded clones specific for bacterial antigens within the human T cell receptor α/β CD48 subset. J. Exp. Med. 177:1763–71 [Google Scholar]
  2. Lantz O, Bendelac A. 2.  1994. An invariant T cell receptor α chain is used by a unique subset of major histocompatibility complex class I–specific CD4+ and CD48 T cells in mice and humans. J. Exp. Med. 180:1097–106 [Google Scholar]
  3. Bendelac A, Killeen N, Littman DR, Schwartz RH. 3.  1994. A subset of CD4+ thymocytes selected by MHC class I molecules. Science 263:1774–78 [Google Scholar]
  4. Bendelac A, Lantz O, Quimby ME, Yewdell JW, Bennink JR, Brutkiewicz RR. 4.  1995. CD1 recognition by mouse NK1+ T lymphocytes. Science 268:863–65 [Google Scholar]
  5. Cerundolo V, Silk JD, Masri SH, Salio M. 5.  2009. Harnessing invariant NKT cells in vaccination strategies. Nat. Rev. Immunol. 9:28–38 [Google Scholar]
  6. Brigl M, Tatituri RV, Watts GF, Bhowruth V, Leadbetter EA. 6.  et al. 2011. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J. Exp. Med. 208:1163–77 [Google Scholar]
  7. Paget C, Mallevaey T, Speak AO, Torres D, Fontaine J. 7.  et al. 2007. Activation of invariant NKT cells by Toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids. Immunity 27:597–609 [Google Scholar]
  8. Salio M, Speak AO, Shepherd D, Polzella P, Illarionov PA. 8.  et al. 2007. Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation. Proc. Natl. Acad. Sci. USA 104:20490–95 [Google Scholar]
  9. Moon JJ, Chu HH, Pepper M, McSorley SJ, Jameson SC. 9.  et al. 2007. Naive CD4+ T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 27:203–13 [Google Scholar]
  10. Van Rhijn I, Kasmar A, de Jong A, Gras S, Bhati M. 10.  et al. 2013. A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nat. Immunol. 14:706–13 [Google Scholar]
  11. Adams EJ, Luoma AM. 11.  2013. The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I-like molecules. Annu. Rev. Immunol. 31:529–61 [Google Scholar]
  12. Zeng Z, Castano AR, Segelke BW, Stura EA, Peterson PA, Wilson IA. 12.  1997. Crystal structure of mouse CD1: An MHC-like fold with a large hydrophobic binding groove. Science 277:339–45 [Google Scholar]
  13. Koch M, Stronge VS, Shepherd D, Gadola SD, Mathew B. 13.  et al. 2005. The crystal structure of human CD1d with and without α-galactosylceramide. Nat. Immunol. 6:819–26 [Google Scholar]
  14. Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB. 14.  et al. 2005. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat. Immunol. 6:810–18 [Google Scholar]
  15. Gadola SD, Zaccai NR, Harlos K, Shepherd D, Castro-Palomino JC. 15.  et al. 2002. Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chains. Nat. Immunol. 3:721–26 [Google Scholar]
  16. Batuwangala T, Shepherd D, Gadola SD, Gibson KJ, Zaccai NR. 16.  et al. 2004. The crystal structure of human CD1b with a bound bacterial glycolipid. J. Immunol. 172:2382–88 [Google Scholar]
  17. Zajonc DM, Elsliger MA, Teyton L, Wilson IA. 17.  2003. Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15 Å. Nat. Immunol. 4:808–15 [Google Scholar]
  18. Zajonc DM, Crispin MD, Bowden TA, Young DC, Cheng TY. 18.  et al. 2005. Molecular mechanism of lipopeptide presentation by CD1a. Immunity 22:209–19 [Google Scholar]
  19. Scharf L, Li NS, Hawk AJ, Garzon D, Zhang T. 19.  et al. 2010. The 2.5 Å structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity 33:853–62 [Google Scholar]
  20. Huang S, Cheng TY, Young DC, Layre E, Madigan CA. 20.  et al. 2011. Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system. Proc. Natl. Acad. Sci. USA 108:19335–40 [Google Scholar]
  21. Garcia-Alles LF, Collmann A, Versluis C, Lindner B, Guiard J. 21.  et al. 2011. Structural reorganization of the antigen-binding groove of human CD1b for presentation of mycobacterial sulfoglycolipids. Proc. Natl. Acad. Sci. USA 108:17755–60 [Google Scholar]
  22. Giabbai B, Sidobre S, Crispin MD, Sanchez-Ruiz Y, Bachi A. 22.  et al. 2005. Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation. J. Immunol. 175:977–84 [Google Scholar]
  23. Lopez-Sagaseta J, Sibener LV, Kung JE, Gumperz J, Adams EJ. 23.  2012. Lysophospholipid presentation by CD1d and recognition by a human natural killer T-cell receptor. EMBO J. 31:2047–59 [Google Scholar]
  24. Aspeslagh S, Li Y, Yu ED, Pauwels N, Trappeniers M. 24.  et al. 2011. Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis. EMBO J. 30:2294–305 [Google Scholar]
  25. East JE, Kennedy AJ, Webb TJ. 25.  2014. Raising the roof: the preferential pharmacological stimulation of Th1 and Th2 responses mediated by NKT cells. Med. Res. Rev 34:45–76 [Google Scholar]
  26. Girardi E, Zajonc DM. 26.  2012. Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells. Immunol. Rev. 250:167–79 [Google Scholar]
  27. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI. 27.  2012. Recognition of CD1d-restricted antigens by natural killer T cells. Nat. Rev. Immunol. 12:845–57 [Google Scholar]
  28. Borg NA, Wun KS, Kjer-Nielsen L, Wilce MC, Pellicci DG. 28.  et al. 2007. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448:44–49 [Google Scholar]
  29. Li Y, Girardi E, Wang J, Yu ED, Painter GF. 29.  et al. 2010. The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode. J. Exp. Med. 207:2383–93 [Google Scholar]
  30. Mallevaey T, Clarke AJ, Scott-Browne JP, Young MH, Roisman LC. 30.  et al. 2011. A molecular basis for NKT cell recognition of CD1d-self-antigen. Immunity 34:315–26 [Google Scholar]
  31. Pellicci DG, Patel O, Kjer-Nielsen L, Pang SS, Sullivan LC. 31.  et al. 2009. Differential recognition of CD1d-α-galactosyl ceramide by the Vβ8.2 and Vβ7 semi-invariant NKT T cell receptors. Immunity 31:47–59 [Google Scholar]
  32. Patel O, Pellicci DG, Uldrich AP, Sullivan LC, Bhati M. 32.  et al. 2011. Vβ2 natural killer T cell antigen receptor-mediated recognition of CD1d-glycolipid antigen. Proc. Natl. Acad. Sci. USA 108:19007–12 [Google Scholar]
  33. Pellicci DG, Clarke AJ, Patel O, Mallevaey T, Beddoe T. 33.  et al. 2011. Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors. Nat. Immunol. 12:827–33 [Google Scholar]
  34. Patel O, Cameron G, Pellicci DG, Liu Z, Byun HS. 34.  et al. 2011. NKT TCR recognition of CD1d-α-C-galactosylceramide. J. Immunol. 187:4705–13 [Google Scholar]
  35. Kerzerho J, Yu ED, Barra CM, Alari-Pahissa E, Girardi E. 35.  et al. 2012. Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties. J. Immunol. 188:2254–65 [Google Scholar]
  36. Girardi E, Yu ED, Li Y, Tarumoto N, Pei B. 36.  et al. 2011. Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for NKT cells. PLoS Biol. 9:e1001189 [Google Scholar]
  37. Yu ED, Girardi E, Wang J, Mac TT, Yu KO. 37.  et al. 2012. Structural basis for the recognition of C20:2-αGalCer by the invariant natural killer T cell receptor-like antibody L363. J. Biol. Chem. 287:1269–78 [Google Scholar]
  38. Lopez-Sagaseta J, Kung JE, Savage PB, Gumperz J, Adams EJ. 38.  2012. The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor. PLoS Biol. 10:e1001412 [Google Scholar]
  39. Zajonc DM, Savage PB, Bendelac A, Wilson IA, Teyton L. 39.  2008. Crystal structures of mouse CD1d-iGb3 complex and its cognate Vα14 T cell receptor suggest a model for dual recognition of foreign and self glycolipids. J. Mol. Biol. 377:1104–16 [Google Scholar]
  40. Yu ED, Girardi E, Wang J, Zajonc DM. 40.  2011. Cutting edge: structural basis for the recognition of β-linked glycolipid antigens by invariant NKT cells. J. Immunol. 187:2079–83 [Google Scholar]
  41. Girardi E, Maricic I, Wang J, Mac TT, Iyer P. 41.  et al. 2012. Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens. Nat. Immunol. 13:851–56 [Google Scholar]
  42. Patel O, Pellicci DG, Gras S, Sandoval-Romero ML, Uldrich AP. 42.  et al. 2012. Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat. Immunol. 13:857–63 [Google Scholar]
  43. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B. 43.  et al. 2012. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491:717–23 [Google Scholar]
  44. Patel O, Kjer-Nielsen L, Le Nours J, Eckle SB, Birkinshaw R. 44.  et al. 2013. Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Nat. Commun. 4:2142 [Google Scholar]
  45. Lopez-Sagaseta J, Dulberger CL, Crooks JE, Parks CD, Luoma AM. 45.  et al. 2013. The molecular basis for mucosal-associated invariant T cell recognition of MR1 proteins. Proc. Natl. Acad. Sci. USA 110:E1771–78 [Google Scholar]
  46. Cohen NR, Garg S, Brenner MB. 46.  2009. Antigen presentation by CD1 lipids, T cells, and NKT cells in microbial immunity. Adv. Immunol. 102:1–94 [Google Scholar]
  47. Barral DC, Brenner MB. 47.  2007. CD1 antigen presentation: how it works. Nat. Rev. Immunol. 7:929–41 [Google Scholar]
  48. Salio M, Silk JD, Cerundolo V. 48.  2010. Recent advances in processing and presentation of CD1 bound lipid antigens. Curr. Opin. Immunol. 22:81–88 [Google Scholar]
  49. De Libero G, Mori L. 49.  2012. Novel insights into lipid antigen presentation. Trends Immunol. 33:103–11 [Google Scholar]
  50. Freigang S, Landais E, Zadorozhny V, Kain L, Yoshida K. 50.  et al. 2012. Scavenger receptors target glycolipids for natural killer T cell activation. J. Clin. Investig. 122:3943–54 [Google Scholar]
  51. van den Elzen P, Garg S, Leon L, Brigl M, Leadbetter EA. 51.  et al. 2005. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature 437:906–10 [Google Scholar]
  52. Freigang S, Kain L, Teyton L. 52.  2013. Transport and uptake of immunogenic lipids. Mol. Immunol. 55:179–81 [Google Scholar]
  53. Bai L, Constantinides MG, Thomas SY, Reboulet R, Meng F. 53.  et al. 2012. Distinct APCs explain the cytokine bias of α-galactosylceramide variants in vivo. J. Immunol. 188:3053–61 [Google Scholar]
  54. Bezbradica JS, Stanic AK, Matsuki N, Bour-Jordan H, Bluestone JA. 54.  et al. 2005. Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J. Immunol. 174:4696–705 [Google Scholar]
  55. Kawasaki N, Vela JL, Nycholat CM, Rademacher C, Khurana A. 55.  et al. 2013. Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation. Proc. Natl. Acad. Sci. USA 110:7826–31 [Google Scholar]
  56. Barral P, Eckl-Dorna J, Harwood NE, De Santo C, Salio M. 56.  et al. 2008. B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc. Natl. Acad. Sci. USA 105:8345–50 [Google Scholar]
  57. Leadbetter EA, Brigl M, Illarionov P, Cohen N, Luteran MC. 57.  et al. 2008. NK T cells provide lipid antigen-specific cognate help for B cells. Proc. Natl. Acad. Sci. USA 105:8339–44 [Google Scholar]
  58. Allan LL, Hoefl K, Zheng DJ, Chung BK, Kozak FK. 58.  et al. 2009. Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells. Blood 114:2411–16 [Google Scholar]
  59. Mukherjee S, Soe TT, Maxfield FR. 59.  1999. Endocytic sorting of lipid analogues differing solely in the chemistry of their hydrophobic tails. J. Cell Biol. 144:1271–84 [Google Scholar]
  60. Odyniec AN, Barral DC, Garg S, Tatituri RV, Besra GS, Brenner MB. 60.  2010. Regulation of CD1 antigen-presenting complex stability. J. Biol. Chem. 285:11937–47 [Google Scholar]
  61. Im JS, Arora P, Bricard G, Molano A, Venkataswamy MM. 61.  et al. 2009. Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation. Immunity 30:888–98 [Google Scholar]
  62. Manolova V, Kistowska M, Paoletti S, Baltariu GM, Bausinger H. 62.  et al. 2006. Functional CD1a is stabilized by exogenous lipids. Eur. J. Immunol. 36:1083–92 [Google Scholar]
  63. Moody DB, Briken V, Cheng TY, Roura-Mir C, Guy MR. 63.  et al. 2002. Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation. Nat. Immunol. 3:435–42 [Google Scholar]
  64. Yu KO, Im JS, Molano A, Dutronc Y, Illarionov PA. 64.  et al. 2005. Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides. Proc. Natl. Acad. Sci. USA 102:3383–88 [Google Scholar]
  65. de la Salle H, Mariotti S, Angenieux C, Gilleron M, Garcia-Alles LF. 65.  et al. 2005. Assistance of microbial glycolipid antigen processing by CD1e. Science 310:1321–24 [Google Scholar]
  66. Prigozy TI, Naidenko O, Qasba P, Elewaut D, Brossay L. 66.  et al. 2001. Glycolipid antigen processing for presentation by CD1d molecules. Science 291:664–67 [Google Scholar]
  67. Zhou D, Mattner J, Cantu C 3rd, Schrantz N, Yin N. 67.  et al. 2004. Lysosomal glycosphingolipid recognition by NKT cells. Science 306:1786–89 [Google Scholar]
  68. Kolter T, Sandhoff K. 68.  2005. Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu. Rev. Cell Dev. Biol. 21:81–103 [Google Scholar]
  69. Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA. 69.  et al. 2004. Saposin C is required for lipid presentation by human CD1b. Nat. Immunol. 5:169–74 [Google Scholar]
  70. Yuan W, Qi X, Tsang P, Kang SJ, Illarionov PA. 70.  et al. 2007. Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules. Proc. Natl. Acad. Sci. USA 104:5551–56 [Google Scholar]
  71. Zhou D, Cantu C 3rd, Sagiv Y, Schrantz N, Kulkarni AB. 71.  et al. 2004. Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science 303:523–27 [Google Scholar]
  72. Facciotti F, Cavallari M, Angenieux C, Garcia-Alles LF, Signorino-Gelo F. 72.  et al. 2011. Fine tuning by human CD1e of lipid-specific immune responses. Proc. Natl. Acad. Sci. USA 108:14228–33 [Google Scholar]
  73. Kang SJ, Cresswell P. 73.  2004. Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to T cells. Nat. Immunol. 5:175–81 [Google Scholar]
  74. Leon L, Tatituri RV, Grenha R, Sun Y, Barral DC. 74.  et al. 2012. Saposins utilize two strategies for lipid transfer and CD1 antigen presentation. Proc. Natl. Acad. Sci. USA 109:4357–64 [Google Scholar]
  75. Schrantz N, Sagiv Y, Liu Y, Savage PB, Bendelac A, Teyton L. 75.  2007. The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells. J. Exp. Med. 204:841–52 [Google Scholar]
  76. Salio M, Ghadbane H, Dushek O, Shepherd D, Cypen J. 76.  et al. 2013. Saposins modulate human invariant natural killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation. Proc. Natl. Acad. Sci. USA 110:E4753–61 [Google Scholar]
  77. Relloso M, Cheng TY, Im JS, Parisini E, Roura-Mir C. 77.  et al. 2008. pH-dependent interdomain tethers of CD1b regulate its antigen capture. Immunity 28:774–86 [Google Scholar]
  78. Bai L, Sagiv Y, Liu Y, Freigang S, Yu KO. 78.  et al. 2009. Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen αGalCer. Proc. Natl. Acad. Sci. USA 106:10254–59 [Google Scholar]
  79. Blum JS, Wearsch PA, Cresswell P. 79.  2013. Pathways of antigen processing. Annu. Rev. Immunol. 31:443–73 [Google Scholar]
  80. Kang SJ, Cresswell P. 80.  2002. Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain. J. Biol. Chem. 277:44838–44 [Google Scholar]
  81. Paduraru C, Spiridon L, Yuan W, Bricard G, Valencia X. 81.  et al. 2006. An N-linked glycan modulates the interaction between the CD1d heavy chain and β2-microglobulin. J. Biol. Chem. 281:40369–78 [Google Scholar]
  82. Zhu Y, Zhang W, Veerapen N, Besra G, Cresswell P. 82.  2010. Calreticulin controls the rate of assembly of CD1d molecules in the endoplasmic reticulum. J. Biol. Chem. 285:38283–92 [Google Scholar]
  83. Kunte A, Zhang W, Paduraru C, Veerapen N, Cox LR. 83.  et al. 2013. Endoplasmic reticulum glycoprotein quality control regulates CD1d assembly and CD1d-mediated antigen presentation. J. Biol. Chem. 288:16391–402 [Google Scholar]
  84. Brozovic S, Nagaishi T, Yoshida M, Betz S, Salas A. 84.  et al. 2004. CD1d function is regulated by microsomal triglyceride transfer protein. Nat. Med. 10:535–39 [Google Scholar]
  85. Dougan SK, Salas A, Rava P, Agyemang A, Kaser A. 85.  et al. 2005. Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. J. Exp. Med. 202:529–39 [Google Scholar]
  86. Zeissig S, Dougan SK, Barral DC, Junker Y, Chen Z. 86.  et al. 2010. Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function. J. Clin. Investig. 120:2889–99 [Google Scholar]
  87. Dougan SK, Rava P, Hussain MM, Blumberg RS. 87.  2007. MTP regulated by an alternate promoter is essential for NKT cell development. J. Exp. Med. 204:533–45 [Google Scholar]
  88. Sagiv Y, Bai L, Wei DG, Agami R, Savage PB. 88.  et al. 2007. A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d. J. Exp. Med. 204:921–28 [Google Scholar]
  89. Kaser A, Hava DL, Dougan SK, Chen Z, Zeissig S. 89.  et al. 2008. Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. Eur. J. Immunol. 38:2351–59 [Google Scholar]
  90. Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. 90.  2001. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity 15:897–908 [Google Scholar]
  91. Kang SJ, Cresswell P. 91.  2002. Regulation of intracellular trafficking of human CD1d by association with MHC class II molecules. EMBO J. 21:1650–60 [Google Scholar]
  92. Barral DC, Cavallari M, McCormick PJ, Garg S, Magee AI. 92.  et al. 2008. CD1a and MHC class I follow a similar endocytic recycling pathway. Traffic 9:1446–57 [Google Scholar]
  93. Barral DC, Garg S, Casalou C, Watts GF, Sandoval JL. 93.  et al. 2012. Arl13b regulates endocytic recycling traffic. Proc. Natl. Acad. Sci. USA 109:21354–59 [Google Scholar]
  94. Garg S, Sharma M, Ung C, Tuli A, Barral DC. 94.  et al. 2011. Lysosomal trafficking, antigen presentation, and microbial killing are controlled by the Arf-like GTPase Arl8b. Immunity 35:182–93 [Google Scholar]
  95. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L. 95.  2004. NKT cells: What's in a name?. Nat. Rev. Immunol. 4:231–37 [Google Scholar]
  96. Brossay L, Chioda M, Burdin N, Koezuka Y, Casorati G. 96.  et al. 1998. CD1d-mediated recognition of an α-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J. Exp. Med. 188:1521–28 [Google Scholar]
  97. Gadola SD, Dulphy N, Salio M, Cerundolo V. 97.  2002. Vα24-JαQ-independent, CD1d-restricted recognition of α-galactosylceramide by human CD4+ and CD8αβ+ T lymphocytes. J. Immunol. 168:5514–20 [Google Scholar]
  98. Brigl M, van den Elzen P, Chen X, Meyers JH, Wu D. 98.  et al. 2006. Conserved and heterogeneous lipid antigen specificities of CD1d-restricted NKT cell receptors. J. Immunol. 176:3625–34 [Google Scholar]
  99. Chang DH, Osman K, Connolly J, Kukreja A, Krasovsky J. 99.  et al. 2005. Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J. Exp. Med. 201:1503–17 [Google Scholar]
  100. Gadola SD, Koch M, Marles-Wright J, Lissin NM, Shepherd D. 100.  et al. 2006. Structure and binding kinetics of three different human CD1d-α-galactosylceramide-specific T cell receptors. J. Exp. Med. 203:699–710 [Google Scholar]
  101. Kjer-Nielsen L, Borg NA, Pellicci DG, Beddoe T, Kostenko L. 101.  et al. 2006. A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition. J. Exp. Med. 203:661–73 [Google Scholar]
  102. Uldrich AP, Patel O, Cameron G, Pellicci DG, Day EB. 102.  et al. 2011. A semi-invariant Vα10+ T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. Nat. Immunol. 12:616–23 [Google Scholar]
  103. Tatituri RV, Watts GF, Bhowruth V, Barton N, Rothchild A. 103.  et al. 2013. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc. Natl. Acad. Sci. USA 110:1827–32 [Google Scholar]
  104. Gapin L, Matsuda JL, Surh CD, Kronenberg M. 104.  2001. NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nat. Immunol. 2:971–78 [Google Scholar]
  105. Hager E, Hawwari A, Matsuda JL, Krangel MS, Gapin L. 105.  2007. Multiple constraints at the level of TCRα rearrangement impact Vα14i NKT cell development. J. Immunol. 179:2228–34 [Google Scholar]
  106. Hu T, Simmons A, Yuan J, Bender TP, Alberola-Ila J. 106.  2010. The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage. Nat. Immunol. 11:435–41 [Google Scholar]
  107. Bezbradica JS, Hill T, Stanic AK, Van Kaer L, Joyce S. 107.  2005. Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc. Natl. Acad. Sci. USA 102:5114–19 [Google Scholar]
  108. Egawa T, Eberl G, Taniuchi I, Benlagha K, Geissmann F. 108.  et al. 2005. Genetic evidence supporting selection of the Vα14i NKT cell lineage from double-positive thymocyte precursors. Immunity 22:705–16 [Google Scholar]
  109. Guo J, Hawwari A, Li H, Sun Z, Mahanta SK. 109.  et al. 2002. Regulation of the TCRα repertoire by the survival window of CD4+CD8+ thymocytes. Nat. Immunol. 3:469–76 [Google Scholar]
  110. D'Cruz LM, Knell J, Fujimoto JK, Goldrath AW. 110.  2010. An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells. Nat. Immunol. 11:240–49 [Google Scholar]
  111. Callen E, Faryabi RB, Luckey M, Hao B, Daniel JA. 111.  et al. 2012. The DNA damage- and transcription-associated protein PAXIP1 controls thymocyte development and emigration. Immunity 37:971–85 [Google Scholar]
  112. Benlagha K, Kyin T, Beavis A, Teyton L, Bendelac A. 112.  2002. A thymic precursor to the NK T cell lineage. Science 296:553–55 [Google Scholar]
  113. Benlagha K, Wei DG, Veiga J, Teyton L, Bendelac A. 113.  2005. Characterization of the early stages of thymic NKT cell development. J. Exp. Med. 202:485–92 [Google Scholar]
  114. Pellicci DG, Hammond KJ, Uldrich AP, Baxter AG, Smyth MJ, Godfrey DI. 114.  2002. A natural killer T (NKT) cell developmental pathway involving a thymus-dependent NK1.1CD4+ CD1d-dependent precursor stage. J. Exp. Med. 195:835–44 [Google Scholar]
  115. Stetson DB, Mohrs M, Reinhardt RL, Baron JL, Wang ZE. 115.  et al. 2003. Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J. Exp. Med. 198:1069–76 [Google Scholar]
  116. Milpied P, Massot B, Renand A, Diem S, Herbelin A. 116.  et al. 2011. IL-17-producing invariant NKT cells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression. Blood 118:2993–3002 [Google Scholar]
  117. McNab FW, Berzins SP, Pellicci DG, Kyparissoudis K, Field K. 117.  et al. 2005. The influence of CD1d in postselection NKT cell maturation and homeostasis. J. Immunol. 175:3762–68 [Google Scholar]
  118. Wei DG, Lee H, Park SH, Beaudoin L, Teyton L. 118.  et al. 2005. Expansion and long-range differentiation of the NKT cell lineage in mice expressing CD1d exclusively on cortical thymocytes. J. Exp. Med. 202:239–48 [Google Scholar]
  119. Berzins SP, McNab FW, Jones CM, Smyth MJ, Godfrey DI. 119.  2006. Long-term retention of mature NK1.1 +NKT cells in the thymus. J. Immunol. 176:4059–65 [Google Scholar]
  120. McNab FW, Pellicci DG, Field K, Besra G, Smyth MJ. 120.  et al. 2007. Peripheral NK1.1 NKT cells are mature and functionally distinct from their thymic counterparts. J. Immunol. 179:6630–37 [Google Scholar]
  121. Matsuda JL, Gapin L, Sidobre S, Kieper WC, Tan JT. 121.  et al. 2002. Homeostasis of Vα14i NKT cells. Nat. Immunol. 3:966–74 [Google Scholar]
  122. Voyle RB, Beermann F, Lees RK, Schumann J, Zimmer J. 122.  et al. 2003. Ligand-dependent inhibition of CD1d-restricted NKT cell development in mice transgenic for the activating receptor Ly49D. J. Exp. Med. 197:919–25 [Google Scholar]
  123. Dose M, Sleckman BP, Han J, Bredemeyer AL, Bendelac A, Gounari F. 123.  2009. Intrathymic proliferation wave essential for Vα14+ natural killer T cell development depends on c-Myc. Proc. Natl. Acad. Sci. USA 106:8641–46 [Google Scholar]
  124. Mycko MP, Ferrero I, Wilson A, Jiang W, Bianchi T. 124.  et al. 2009. Selective requirement for c-Myc at an early stage of Vα14i NKT cell development. J. Immunol. 182:4641–48 [Google Scholar]
  125. Townsend MJ, Weinmann AS, Matsuda JL, Salomon R, Farnham PJ. 125.  et al. 2004. T-bet regulates the terminal maturation and homeostasis of NK and Vα14i NKT cells. Immunity 20:477–94 [Google Scholar]
  126. Monticelli LA, Yang Y, Knell J, D'Cruz LM, Cannarile MA. 126.  et al. 2009. Transcriptional regulator Id2 controls survival of hepatic NKT cells. Proc. Natl. Acad. Sci. USA 106:19461–66 [Google Scholar]
  127. van Gisbergen KP, Kragten NA, Hertoghs KM, Wensveen FM, Jonjic S. 127.  et al. 2012. Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation. Nat. Immunol. 13:864–71 [Google Scholar]
  128. Benlagha K, Bendelac A. 128.  2000. CD1d-restricted mouse Vα14 and human Vα24 T cells: lymphocytes of innate immunity. Semin. Immunol. 12:537–42 [Google Scholar]
  129. Matsuda JL, Naidenko OV, Gapin L, Nakayama T, Taniguchi M. 129.  et al. 2000. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J. Exp. Med. 192:741–54 [Google Scholar]
  130. Engel I, Hammond K, Sullivan BA, He X, Taniuchi I. 130.  et al. 2010. Co-receptor choice by Vα14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection. J. Exp. Med. 207:1015–29 [Google Scholar]
  131. He X, He X, Dave VP, Zhang Y, Hua X. 131.  et al. 2005. The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature 433:826–33 [Google Scholar]
  132. Engel I, Zhao M, Kappes D, Taniuchi I, Kronenberg M. 132.  2012. The transcription factor Th-POK negatively regulates Th17 differentiation in Vα14i NKT cells. Blood 120:4524–32 [Google Scholar]
  133. Wang L, Carr T, Xiong Y, Wildt KF, Zhu J. 133.  et al. 2010. The sequential activity of Gata3 and Thpok is required for the differentiation of CD1d-restricted CD4+ NKT cells. Eur. J. Immunol. 40:2385–90 [Google Scholar]
  134. Kim PJ, Pai SY, Brigl M, Besra GS, Gumperz J, Ho IC. 134.  2006. GATA-3 regulates the development and function of invariant NKT cells. J. Immunol. 177:6650–59 [Google Scholar]
  135. Enders A, Stankovic S, Teh C, Uldrich AP, Yabas M. 135.  et al. 2012. ZBTB7B (Th-POK) regulates the development of IL-17-producing CD1d-restricted mouse NKT cells. J. Immunol. 189:5240–49 [Google Scholar]
  136. Michel ML, Mendes-da-Cruz D, Keller AC, Lochner M, Schneider E. 136.  et al. 2008. Critical role of ROR-γt in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. Proc. Natl. Acad. Sci. USA 105:19845–50 [Google Scholar]
  137. Napolitano A, Pittoni P, Beaudoin L, Lehuen A, Voehringer D. 137.  et al. 2013. Functional education of invariant NKT cells by dendritic cell tuning of SHP-1. J. Immunol. 190:3299–308 [Google Scholar]
  138. Moran AE, Holzapfel KL, Xing Y, Cunningham NR, Maltzman JS. 138.  et al. 2011. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208:1279–89 [Google Scholar]
  139. Qiao Y, Zhu L, Sofi H, Lapinski PE, Horai R. 139.  et al. 2012. Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells requires stronger T-cell receptor signals than conventional CD4 T cells. Proc. Natl. Acad. Sci. USA 109:16264–69 [Google Scholar]
  140. Zietara N, Lyszkiewicz M, Witzlau K, Naumann R, Hurwitz R. 140.  et al. 2013. Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells. Proc. Natl. Acad. Sci. USA 110:7407–12 [Google Scholar]
  141. Fedeli M, Napolitano A, Wong MP, Marcais A, de Lalla C. 141.  et al. 2009. Dicer-dependent microRNA pathway controls invariant NKT cell development. J. Immunol. 183:2506–12 [Google Scholar]
  142. Zheng Q, Zhou L, Mi QS. 142.  2012. MicroRNA miR-150 is involved in Vα14 invariant NKT cell development and function. J. Immunol. 188:2118–26 [Google Scholar]
  143. Zhou L, Seo KH, He HZ, Pacholczyk R, Meng DM. 143.  et al. 2009. Tie2cre-induced inactivation of the miRNA-processing enzyme Dicer disrupts invariant NKT cell development. Proc. Natl. Acad. Sci. USA 106:10266–71 [Google Scholar]
  144. Bezman NA, Chakraborty T, Bender T, Lanier LL. 144.  2011. miR-150 regulates the development of NK and iNKT cells. J. Exp. Med. 208:2717–31 [Google Scholar]
  145. Chun T, Page MJ, Gapin L, Matsuda JL, Xu H. 145.  et al. 2003. CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells. J. Exp. Med. 197:907–18 [Google Scholar]
  146. Pellicci DG, Uldrich AP, Kyparissoudis K, Crowe NY, Brooks AG. 146.  et al. 2003. Intrathymic NKT cell development is blocked by the presence of α-galactosylceramide. Eur. J. Immunol. 33:1816–23 [Google Scholar]
  147. Schumann J, Pittoni P, Tonti E, Macdonald HR, Dellabona P, Casorati G. 147.  2005. Targeted expression of human CD1d in transgenic mice reveals independent roles for thymocytes and thymic APCs in positive and negative selection of Vα14i NKT cells. J. Immunol. 175:7303–10 [Google Scholar]
  148. Schumann J, Voyle RB, Wei BY, MacDonald HR. 148.  2003. Cutting edge: influence of the TCR Vβ domain on the avidity of CD1d:α-galactosylceramide binding by invariant Vα14 NKT cells. J. Immunol. 170:5815–19 [Google Scholar]
  149. Schumann J, Mycko MP, Dellabona P, Casorati G, MacDonald HR. 149.  2006. Cutting edge: influence of the TCR Vβ domain on the selection of semi-invariant NKT cells by endogenous ligands. J. Immunol. 176:2064–68 [Google Scholar]
  150. Wei DG, Curran SA, Savage PB, Teyton L, Bendelac A. 150.  2006. Mechanisms imposing the Vβ bias of Vα14 natural killer T cells and consequences for microbial glycolipid recognition. J. Exp. Med. 203:1197–207 [Google Scholar]
  151. Stanic AK, Shashidharamurthy R, Bezbradica JS, Matsuki N, Yoshimura Y. 151.  et al. 2003. Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected]. J. Immunol. 171:4539–51 [Google Scholar]
  152. Iezzi G, Karjalainen K, Lanzavecchia A. 152.  1998. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8:89–95 [Google Scholar]
  153. Matsuda JL, Gapin L, Baron JL, Sidobre S, Stetson DB. 153.  et al. 2003. Mouse Vα14i natural killer T cells are resistant to cytokine polarization in vivo. Proc. Natl. Acad. Sci. USA 100:8395–400 [Google Scholar]
  154. Park SH, Benlagha K, Lee D, Balish E, Bendelac A. 154.  2000. Unaltered phenotype, tissue distribution and function of Vα14+ NKT cells in germ-free mice. Eur. J. Immunol. 30:620–25 [Google Scholar]
  155. D'Andrea A, Goux D, De Lalla C, Koezuka Y, Montagna D. 155.  et al. 2000. Neonatal invariant Vα24+ NKT lymphocytes are activated memory cells. Eur. J. Immunol. 30:1544–50 [Google Scholar]
  156. van Der Vliet HJ, Nishi N, de Gruijl TD, von Blomberg BM, van den Eertwegh AJ. 156.  et al. 2000. Human natural killer T cells acquire a memory-activated phenotype before birth. Blood 95:2440–42 [Google Scholar]
  157. Eberl G, Lowin-Kropf B, MacDonald HR. 157.  1999. Cutting edge: NKT cell development is selectively impaired in Fyn-deficient mice. J. Immunol. 163:4091–94 [Google Scholar]
  158. Gadue P, Morton N, Stein PL. 158.  1999. The Src family tyrosine kinase Fyn regulates natural killer T cell development. J. Exp. Med. 190:1189–96 [Google Scholar]
  159. Veillette A. 159.  2006. Immune regulation by SLAM family receptors and SAP-related adaptors. Nat. Rev. Immunol. 6:56–66 [Google Scholar]
  160. Chung B, Aoukaty A, Dutz J, Terhorst C, Tan R. 160.  2005. Signaling lymphocytic activation molecule-associated protein controls NKT cell functions. J. Immunol. 174:3153–57 [Google Scholar]
  161. Nichols KE, Hom J, Gong SY, Ganguly A, Ma CS. 161.  et al. 2005. Regulation of NKT cell development by SAP, the protein defective in XLP. Nat. Med. 11:340–45 [Google Scholar]
  162. Pasquier B, Yin L, Fondaneche MC, Relouzat F, Bloch-Queyrat C. 162.  et al. 2005. Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product. J. Exp. Med. 201:695–701 [Google Scholar]
  163. Rigaud S, Fondaneche MC, Lambert N, Pasquier B, Mateo V. 163.  et al. 2006. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature 444:110–14 [Google Scholar]
  164. Griewank K, Borowski C, Rietdijk S, Wang N, Julien A. 164.  et al. 2007. Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development. Immunity 27:751–62 [Google Scholar]
  165. Jordan MA, Fletcher JM, Pellicci D, Baxter AG. 165.  2007. Slamf1, the NKT cell control gene Nkt1. J. Immunol. 178:1618–27 [Google Scholar]
  166. Horai R, Mueller KL, Handon RA, Cannons JL, Anderson SM. 166.  et al. 2007. Requirements for selection of conventional and innate T lymphocyte lineages. Immunity 27:775–85 [Google Scholar]
  167. Choi EY, Jung KC, Park HJ, Chung DH, Song JS. 167.  et al. 2005. Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells. Immunity 23:387–96 [Google Scholar]
  168. Li W, Kim MG, Gourley TS, McCarthy BP, Sant'Angelo DB, Chang CH. 168.  2005. An alternate pathway for CD4 T cell development: thymocyte-expressed MHC class II selects a distinct T cell population. Immunity 23:375–86 [Google Scholar]
  169. Li W, Sofi MH, Yeh N, Sehra S, McCarthy BP. 169.  et al. 2007. Thymic selection pathway regulates the effector function of CD4 T cells. J. Exp. Med. 204:2145–57 [Google Scholar]
  170. Latour S, Gish G, Helgason CD, Humphries RK, Pawson T, Veillette A. 170.  2001. Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product. Nat. Immunol. 2:681–90 [Google Scholar]
  171. Cannons JL, Yu LJ, Hill B, Mijares LA, Dombroski D. 171.  et al. 2004. SAP regulates TH2 differentiation and PKC-θ-mediated activation of NF-κB1. Immunity 21:693–706 [Google Scholar]
  172. Stanic AK, Bezbradica JS, Park JJ, Van Kaer L, Boothby MR, Joyce S. 172.  2004. Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase Cθ and NF-κB. J. Immunol. 172:4667–71 [Google Scholar]
  173. Kovalovsky D, Uche OU, Eladad S, Hobbs RM, Yi W. 173.  et al. 2008. The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nat. Immunol. 9:1055–64 [Google Scholar]
  174. Savage AK, Constantinides MG, Han J, Picard D, Martin E. 174.  et al. 2008. The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity 29:391–403 [Google Scholar]
  175. Lazarevic V, Zullo AJ, Schweitzer MN, Staton TL, Gallo EM. 175.  et al. 2009. The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cells. Nat. Immunol. 10:306–13 [Google Scholar]
  176. Seiler MP, Mathew R, Liszewski MK, Spooner CJ, Barr K. 176.  et al. 2012. Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling. Nat. Immunol. 13:264–71 [Google Scholar]
  177. Kovalovsky D, Alonzo ES, Uche OU, Eidson M, Nichols KE, Sant'Angelo DB. 177.  2010. PLZF induces the spontaneous acquisition of memory/effector functions in T cells independently of NKT cell-related signals. J. Immunol. 184:6746–55 [Google Scholar]
  178. Kreslavsky T, Savage AK, Hobbs R, Gounari F, Bronson R. 178.  et al. 2009. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of γδ T cells with restricted TCR diversity. Proc. Natl. Acad. Sci. USA 106:12453–58 [Google Scholar]
  179. Savage AK, Constantinides MG, Bendelac A. 179.  2011. Promyelocytic leukemia zinc finger turns on the effector T cell program without requirement for agonist TCR signaling. J. Immunol. 186:5801–6 [Google Scholar]
  180. Thomas SY, Scanlon ST, Griewank KG, Constantinides MG, Savage AK. 180.  et al. 2011. PLZF induces an intravascular surveillance program mediated by long-lived LFA-1-ICAM-1 interactions. J. Exp. Med. 208:1179–88 [Google Scholar]
  181. Gleimer M, von Boehmer H, Kreslavsky T. 181.  2012. PLZF controls the expression of a limited number of genes essential for NKT cell function. Front. Immunol. 3:374 [Google Scholar]
  182. Mathew R, Seiler MP, Scanlon ST, Mao AP, Constantinides MG. 182.  et al. 2012. BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs. Nature 491:618–21 [Google Scholar]
  183. Cohen NR, Brennan PJ, Shay T, Watts GF, Brigl M. 183.  et al. 2013. Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat. Immunol. 14:90–99 [Google Scholar]
  184. Shen S, Wu J, Srivatsan S, Gorentla BK, Shin J. 184.  et al. 2011. Tight regulation of diacylglycerol-mediated signaling is critical for proper invariant NKT cell development. J. Immunol. 187:2122–29 [Google Scholar]
  185. Lee AJ, Zhou X, Chang M, Hunzeker J, Bonneau RH. 185.  et al. 2010. Regulation of natural killer T-cell development by deubiquitinase CYLD. EMBO J. 29:1600–12 [Google Scholar]
  186. Chiu YH, Park SH, Benlagha K, Forestier C, Jayawardena-Wolf J. 186.  et al. 2002. Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail-truncated CD1d. Nat. Immunol. 3:55–60 [Google Scholar]
  187. Gadola SD, Silk JD, Jeans A, Illarionov PA, Salio M. 187.  et al. 2006. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J. Exp. Med. 203:2293–303 [Google Scholar]
  188. Schumann J, Facciotti F, Panza L, Michieletti M, Compostella F. 188.  et al. 2007. Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolism. Eur. J. Immunol. 37:1431–41 [Google Scholar]
  189. Sagiv Y, Hudspeth K, Mattner J, Schrantz N, Stern RK. 189.  et al. 2006. Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein. J. Immunol. 177:26–30 [Google Scholar]
  190. Kolter T, Sandhoff K. 190.  2006. Sphingolipid metabolism diseases. Biochim. Biophys. Acta 1758:2057–79 [Google Scholar]
  191. Stanic AK, De Silva AD, Park JJ, Sriram V, Ichikawa S. 191.  et al. 2003. Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by β-d-glucosylceramide synthase deficiency. Proc. Natl. Acad. Sci. USA 100:1849–54 [Google Scholar]
  192. Brennan PJ, Tatituri RV, Brigl M, Kim EY, Tuli A. 192.  et al. 2011. Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat. Immunol. 12:1202–11 [Google Scholar]
  193. Yamashita T, Wada R, Sasaki T, Deng C, Bierfreund U. 193.  et al. 1999. A vital role for glycosphingolipid synthesis during development and differentiation. Proc. Natl. Acad. Sci. USA 96:9142–47 [Google Scholar]
  194. Facciotti F, Ramanjaneyulu GS, Lepore M, Sansano S, Cavallari M. 194.  et al. 2012. Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nat. Immunol. 13:474–80 [Google Scholar]
  195. Xia C, Yao Q, Schumann J, Rossy E, Chen W. 195.  et al. 2006. Synthesis and biological evaluation of α-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3). Bioorgan. Med. Chem. Lett. 16:2195–99 [Google Scholar]
  196. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd. 196.  et al. 2005. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525–29 [Google Scholar]
  197. Porubsky S, Speak AO, Luckow B, Cerundolo V, Platt FM, Grone HJ. 197.  2007. Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency. Proc. Natl. Acad. Sci. USA 104:5977–82 [Google Scholar]
  198. Li Y, Thapa P, Hawke D, Kondo Y, Furukawa K. 198.  et al. 2009. Immunologic glycosphingolipidomics and NKT cell development in mouse thymus. J. Proteome Res. 8:2740–51 [Google Scholar]
  199. Porubsky S, Speak AO, Salio M, Jennemann R, Bonrouhi M. 199.  et al. 2012. Globosides but not isoglobosides can impact the development of invariant NKT cells and their interaction with dendritic cells. J. Immunol. 189:3007–17 [Google Scholar]
  200. Milland J, Christiansen D, Lazarus BD, Taylor SG, Xing PX, Sandrin MS. 200.  2006. The molecular basis for Galα(1,3)Gal expression in animals with a deletion of the α1,3galactosyltransferase gene. J. Immunol. 176:2448–54 [Google Scholar]
  201. Paduraru C, Bezbradica JS, Kunte A, Kelly R, Shayman JA. 201.  et al. 2013. Role for lysosomal phospholipase A2 in iNKT cell-mediated CD1d recognition. Proc. Natl. Acad. Sci. USA 110:5097–102 [Google Scholar]
  202. Chang DH, Deng H, Matthews P, Krasovsky J, Ragupathi G. 202.  et al. 2008. Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer. Blood 112:1308–16 [Google Scholar]
  203. Cox D, Fox L, Tian R, Bardet W, Skaley M. 203.  et al. 2009. Determination of cellular lipids bound to human CD1d molecules. PLoS ONE 4:e5325 [Google Scholar]
  204. Yuan W, Kang SJ, Evans JE, Cresswell P. 204.  2009. Natural lipid ligands associated with human CD1d targeted to different subcellular compartments. J. Immunol. 182:4784–91 [Google Scholar]
  205. Fox LM, Cox DG, Lockridge JL, Wang X, Chen X. 205.  et al. 2009. Recognition of lyso-phospholipids by human natural killer T lymphocytes. PLoS Biol. 7:e1000228 [Google Scholar]
  206. Zeissig S, Murata K, Sweet L, Publicover J, Hu Z. 206.  et al. 2012. Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat. Med. 18:1060–68 [Google Scholar]
  207. Albu DI, VanValkenburgh J, Morin N, Califano D, Jenkins NA. 207.  et al. 2011. Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes. Proc. Natl. Acad. Sci. USA 108:6211–16 [Google Scholar]
  208. Benlagha K, Weiss A, Beavis A, Teyton L, Bendelac A. 208.  2000. In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. J. Exp. Med. 191:1895–903 [Google Scholar]
  209. Doisne JM, Becourt C, Amniai L, Duarte N, Le Luduec JB. 209.  et al. 2009. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor γt+ and respond preferentially under inflammatory conditions. J. Immunol. 183:2142–49 [Google Scholar]
  210. Doisne JM, Soulard V, Becourt C, Amniai L, Henrot P. 210.  et al. 2011. Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria. J. Immunol. 186:662–66 [Google Scholar]
  211. Wong CH, Kubes P. 211.  2013. Imaging natural killer T cells in action. Immunol. Cell Biol. 91:304–10 [Google Scholar]
  212. Barral P, Sanchez-Nino MD, van Rooijen N, Cerundolo V, Batista FD. 212.  2012. The location of splenic NKT cells favours their rapid activation by blood-borne antigen. EMBO J. 31:2378–90 [Google Scholar]
  213. King IL, Amiel E, Tighe M, Mohrs K, Veerapen N. 213.  et al. 2013. The mechanism of splenic invariant NKT cell activation dictates localization in vivo. J. Immunol. 191:572–82 [Google Scholar]
  214. Batista FD, Harwood NE. 214.  2009. The who, how, and where of antigen presentation to B cells. Nat. Rev. Immunol. 9:15–27 [Google Scholar]
  215. Cerundolo V, Barral P, Batista FD. 215.  2010. Synthetic iNKT cell-agonists as vaccine adjuvants—finding the balance. Curr. Opin. Immunol. 22:417–24 [Google Scholar]
  216. Lee WY, Moriarty TJ, Wong CH, Zhou H, Strieter RM. 216.  et al. 2010. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat. Immunol. 11:295–302 [Google Scholar]
  217. Velazquez P, Cameron TO, Kinjo Y, Nagarajan N, Kronenberg M, Dustin ML. 217.  2008. Cutting edge: activation by innate cytokines or microbial antigens can cause arrest of natural killer T cell patrolling of liver sinusoids. J. Immunol. 180:2024–28 [Google Scholar]
  218. Geissmann F, Cameron TO, Sidobre S, Manlongat N, Kronenberg M. 218.  et al. 2005. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol. 3:e113 [Google Scholar]
  219. Scanlon ST, Thomas SY, Ferreira CM, Bai L, Krausz T. 219.  et al. 2011. Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation. J. Exp. Med. 208:2113–24 [Google Scholar]
  220. Wingender G, Rogers P, Batzer G, Lee MS, Bai D. 220.  et al. 2011. Invariant NKT cells are required for airway inflammation induced by environmental antigens. J. Exp. Med. 208:1151–62 [Google Scholar]
  221. Kawakami K, Yamamoto N, Kinjo Y, Miyagi K, Nakasone C. 221.  et al. 2003. Critical role of Vα14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection. Eur. J. Immunol. 33:3322–30 [Google Scholar]
  222. Nieuwenhuis EE, Matsumoto T, Exley M, Schleipman RA, Glickman J. 222.  et al. 2002. CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat. Med. 8:588–93 [Google Scholar]
  223. Kastenmuller W, Torabi-Parizi P, Subramanian N, Lammermann T, Germain RN. 223.  2012. A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell 150:1235–48 [Google Scholar]
  224. Barral P, Polzella P, Bruckbauer A, van Rooijen N, Besra GS. 224.  et al. 2010. CD169+ macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes. Nat. Immunol. 11:303–12 [Google Scholar]
  225. Wong CH, Jenne CN, Lee WY, Leger C, Kubes P. 225.  2011. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science 334:101–5 [Google Scholar]
  226. Germain RN, Robey EA, Cahalan MD. 226.  2012. A decade of imaging cellular motility and interaction dynamics in the immune system. Science 336:1676–81 [Google Scholar]
  227. Natori T, Koezuka Y, Higa T. 227.  1993. Agelasphins, novel α-galactosylceramides from the marine sponge Agelas mauritianus. Tetrahedron Lett. 34:5591–92 [Google Scholar]
  228. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y. 228.  et al. 1997. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278:1626–29 [Google Scholar]
  229. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R. 229.  et al. 2006. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat. Immunol. 7:978–86 [Google Scholar]
  230. Kinjo Y, Wu D, Kim G, Xing GW, Poles MA. 230.  et al. 2005. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434:520–25 [Google Scholar]
  231. Sriram V, Du W, Gervay-Hague J, Brutkiewicz RR. 231.  2005. Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. Eur. J. Immunol. 35:1692–701 [Google Scholar]
  232. Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E. 232.  et al. 2011. Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. Nat. Immunol. 12:966–74 [Google Scholar]
  233. Cohen NR, Tatituri RV, Rivera A, Watts GF, Kim EY. 233.  et al. 2011. Innate recognition of cell wall beta-glucans drives invariant natural killer T cell responses against fungi. Cell Host Microbe 10:437–50 [Google Scholar]
  234. Tyznik AJ, Tupin E, Nagarajan NA, Her MJ, Benedict CA, Kronenberg M. 234.  2008. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J. Immunol. 181:4452–56 [Google Scholar]
  235. Nagarajan NA, Kronenberg M. 235.  2007. Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J. Immunol. 178:2706–13 [Google Scholar]
  236. Rachitskaya AV, Hansen AM, Horai R, Li Z, Villasmil R. 236.  et al. 2008. Cutting edge: NKT cells constitutively express IL-23 receptor and RORγt and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J. Immunol. 180:5167–71 [Google Scholar]
  237. Terashima A, Watarai H, Inoue S, Sekine E, Nakagawa R. 237.  et al. 2008. A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. J. Exp. Med. 205:2727–33 [Google Scholar]
  238. Germain C, Meier A, Jensen T, Knapnougel P, Poupon G. 238.  et al. 2011. Induction of lectin-like transcript 1 (LLT1) protein cell surface expression by pathogens and interferon-γ contributes to modulate immune responses. J. Biol. Chem. 286:37964–75 [Google Scholar]
  239. Kuylenstierna C, Bjorkstrom NK, Andersson SK, Sahlstrom P, Bosnjak L. 239.  et al. 2011. NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d. Eur. J. Immunol. 41:1913–23 [Google Scholar]
  240. Wang X, Bishop KA, Hegde S, Rodenkirch LA, Pike JW, Gumperz JE. 240.  2012. Human invariant natural killer T cells acquire transient innate responsiveness via histone H4 acetylation induced by weak TCR stimulation. J. Exp. Med. 209:987–1000 [Google Scholar]
  241. Bendelac A, Bonneville M, Kearney JF. 241.  2001. Autoreactivity by design: innate B and T lymphocytes. Nat. Rev. Immunol. 1:177–86 [Google Scholar]
  242. Skold M, Xiong X, Illarionov PA, Besra GS, Behar SM. 242.  2005. Interplay of cytokines and microbial signals in regulation of CD1d expression and NKT cell activation. J. Immunol. 175:3584–93 [Google Scholar]
  243. Raghuraman G, Geng Y, Wang CR. 243.  2006. IFN-β-mediated up-regulation of CD1d in bacteria-infected APCs. J. Immunol. 177:7841–48 [Google Scholar]
  244. Raftery MJ, Winau F, Giese T, Kaufmann SH, Schaible UE, Schonrich G. 244.  2008. Viral danger signals control CD1d de novo synthesis and NKT cell activation. Eur. J. Immunol. 38:668–79 [Google Scholar]
  245. Roura-Mir C, Wang L, Cheng TY, Matsunaga I, Dascher CC. 245.  et al. 2005. Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2. J. Immunol. 175:1758–66 [Google Scholar]
  246. Yakimchuk K, Roura-Mir C, Magalhaes KG, de Jong A, Kasmar AG. 246.  et al. 2011. Borrelia burgdorferi infection regulates CD1 expression in human cells and tissues via IL1-β. Eur. J. Immunol. 41:694–705 [Google Scholar]
  247. Kinjo Y, Pei B, Bufali S, Raju R, Richardson SK. 247.  et al. 2008. Natural Sphingomonas glycolipids vary greatly in their ability to activate natural killer T cells. Chem. Biol. 15:654–64 [Google Scholar]
  248. Sanderson JP, Waldburger-Hauri K, Garzon D, Matulis G, Mansour S. 248.  et al. 2012. Natural variations at position 93 of the invariant Vα24-Jα18 α chain of human iNKT-cell TCRs strongly impact on CD1d binding. Eur. J. Immunol. 42:248–55 [Google Scholar]
  249. Pei B, Speak AO, Shepherd D, Butters T, Cerundolo V. 249.  et al. 2011. Diverse endogenous antigens for mouse NKT cells: self-antigens that are not glycosphingolipids. J. Immunol. 186:1348–160 [Google Scholar]
  250. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T. 250.  et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–98 [Google Scholar]
  251. Wingender G, Stepniak D, Krebs P, Lin L, McBride S. 251.  et al. 2012. Intestinal microbes affect phenotypes and functions of invariant natural killer T cells in mice. Gastroenterology 143:418–28 [Google Scholar]
  252. Nieuwenhuis EE, Matsumoto T, Lindenbergh D, Willemsen R, Kaser A. 252.  et al. 2009. Cd1d-dependent regulation of bacterial colonization in the intestine of mice. J. Clin. Investig. 119:1241–50 [Google Scholar]
  253. Olszak T, An D, Zeissig S, Vera MP, Richter J. 253.  et al. 2012. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336:489–93 [Google Scholar]
  254. Wieland Brown LC, Penaranda C, Kashyap PC, Williams BB, Clardy J. 254.  et al. 2013. Production of α-galactosylceramide by a prominent member of the human gut microbiota. PLoS Biol. 11:e1001610 [Google Scholar]
  255. Chang YJ, Kim HY, Albacker LA, Lee HH, Baumgarth N. 255.  et al. 2011. Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J. Clin. Investig. 121:57–69 [Google Scholar]
  256. Cerundolo V, Salio M. 256.  2007. Harnessing NKT cells for therapeutic applications. Curr. Top. Microbiol. Immunol. 314:325–40 [Google Scholar]
  257. Galli G, Nuti S, Tavarini S, Galli-Stampino L, De Lalla C. 257.  et al. 2003. CD1d-restricted help to B cells by human invariant natural killer T lymphocytes. J. Exp. Med. 197:1051–57 [Google Scholar]
  258. Tonti E, Galli G, Malzone C, Abrignani S, Casorati G, Dellabona P. 258.  2009. NKT-cell help to B lymphocytes can occur independently of cognate interaction. Blood 113:370–76 [Google Scholar]
  259. Galli G, Pittoni P, Tonti E, Malzone C, Uematsu Y. 259.  et al. 2007. Invariant NKT cells sustain specific B cell responses and memory. Proc. Natl. Acad. Sci. USA 104:3984–89 [Google Scholar]
  260. Chang PP, Barral P, Fitch J, Pratama A, Ma CS. 260.  et al. 2012. Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses. Nat. Immunol. 13:35–43 [Google Scholar]
  261. King IL, Fortier A, Tighe M, Dibble J, Watts GF. 261.  et al. 2012. Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. Nat. Immunol. 13:44–50 [Google Scholar]
  262. Tonti E, Fedeli M, Napolitano A, Iannacone M, von Andrian UH. 262.  et al. 2012. Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4+ T cell help. J. Immunol. 188:3217–22 [Google Scholar]
  263. Bosma A, Abdel-Gadir A, Isenberg DA, Jury EC, Mauri C. 263.  2012. Lipid-antigen presentation by CD1d+ B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36:477–90 [Google Scholar]
  264. Carnaud C, Lee D, Donnars O, Park SH, Beavis A. 264.  et al. 1999. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J. Immunol. 163:4647–50 [Google Scholar]
  265. Schmieg J, Yang G, Franck RW, Tsuji M. 265.  2003. Superior protection against malaria and melanoma metastases by a C-glycoside analogue of the natural killer T cell ligand α-Galactosylceramide. J. Exp. Med. 198:1631–41 [Google Scholar]
  266. Iwamura C, Shinoda K, Endo Y, Watanabe Y, Tumes DJ. 266.  et al. 2012. Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo. Proc. Natl. Acad. Sci. USA 109:16992–97 [Google Scholar]
  267. Lynch L, Nowak M, Varghese B, Clark J, Hogan AE. 267.  et al. 2012. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37:574–87 [Google Scholar]
  268. Lynch L, O'Shea D, Winter DC, Geoghegan J, Doherty DG, O'Farrelly C. 268.  2009. Invariant NKT cells and CD1d+ cells amass in human omentum and are depleted in patients with cancer and obesity. Eur. J. Immunol. 39:1893–901 [Google Scholar]
  269. Ji Y, Sun S, Xu A, Bhargava P, Yang L. 269.  et al. 2012. Activation of natural killer T cells promotes M2 Macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity. J. Biol. Chem. 287:13561–71 [Google Scholar]
  270. Schipper HS, Rakhshandehroo M, van de Graaf SF, Venken K, Koppen A. 270.  et al. 2012. Natural killer T cells in adipose tissue prevent insulin resistance. J. Clin. Investig. 122:3343–54 [Google Scholar]
  271. Kotas ME, Lee HY, Gillum MP, Annicelli C, Guigni BA. 271.  et al. 2011. Impact of CD1d deficiency on metabolism. PLoS ONE 6:e25478 [Google Scholar]
  272. Wu L, Parekh VV, Gabriel CL, Bracy DP, Marks-Shulman PA. 272.  et al. 2012. Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice. Proc. Natl. Acad. Sci. USA 109:E1143–52 [Google Scholar]
  273. Semmling V, Lukacs-Kornek V, Thaiss CA, Quast T, Hochheiser K. 273.  et al. 2010. Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs. Nat. Immunol. 11:313–20 [Google Scholar]
  274. Fujii S, Shimizu K, Hemmi H, Fukui M, Bonito AJ. 274.  et al. 2006. Glycolipid α-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice. Proc. Natl. Acad. Sci. USA 103:11252–57 [Google Scholar]
  275. Fujii S, Shimizu K, Smith C, Bonifaz L, Steinman RM. 275.  2003. Activation of natural killer T cells by α-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein. J. Exp. Med. 198:267–79 [Google Scholar]
  276. Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B. 276.  et al. 2003. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J. Immunol. 171:5140–47 [Google Scholar]
  277. Silk JD, Hermans IF, Gileadi U, Chong TW, Shepherd D. 277.  et al. 2004. Utilizing the adjuvant properties of CD1d-dependent NK T cells in T cell-mediated immunotherapy. J. Clin. Investig. 114:1800–11 [Google Scholar]
  278. Hegde S, Jankowska-Gan E, Roenneburg DA, Torrealba J, Burlingham WJ, Gumperz JE. 278.  2009. Human NKT cells promote monocyte differentiation into suppressive myeloid antigen-presenting cells. J. Leukoc. Biol. 86:757–68 [Google Scholar]
  279. De Santo C, Salio M, Masri SH, Lee LY, Dong T. 279.  et al. 2008. Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J. Clin. Investig. 118:4036–48 [Google Scholar]
  280. Paget C, Ivanov S, Fontaine J, Blanc F, Pichavant M. 280.  et al. 2011. Potential role of invariant NKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia. J. Immunol. 186:5590–602 [Google Scholar]
  281. Kok WL, Denney L, Benam K, Cole S, Clelland C. 281.  et al. 2012. Pivotal advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. J. Leukoc. Biol. 91:357–68 [Google Scholar]
  282. Paget C, Ivanov S, Fontaine J, Renneson J, Blanc F. 282.  et al. 2012. Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J. Biol. Chem. 287:8816–29 [Google Scholar]
  283. Bedel R, Matsuda JL, Brigl M, White J, Kappler J. 283.  et al. 2012. Lower TCR repertoire diversity in Traj18-deficient mice. Nat. Immunol. 13:705–6 [Google Scholar]
  284. Ho LP, Denney L, Luhn K, Teoh D, Clelland C, McMichael AJ. 284.  2008. Activation of invariant NKT cells enhances the innate immune response and improves the disease course in influenza A virus infection. Eur. J. Immunol. 38:1913–22 [Google Scholar]
  285. Parekh VV, Wu L, Olivares-Villagomez D, Wilson KT, Van Kaer L. 285.  2013. Activated invariant NKT cells control central nervous system autoimmunity in a mechanism that involves myeloid-derived suppressor cells. J. Immunol. 190:1948–60 [Google Scholar]
  286. Denney L, Kok WL, Cole SL, Sanderson S, McMichael AJ, Ho LP. 286.  2012. Activation of invariant NKT cells in early phase of experimental autoimmune encephalomyelitis results in differentiation of Ly6Chi inflammatory monocyte to M2 macrophages and improved outcome. J. Immunol. 189:551–57 [Google Scholar]
  287. Kim EY, Battaile JT, Patel AC, You Y, Agapov E. 287.  et al. 2008. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat. Med. 14:633–40 [Google Scholar]
  288. Broxmeyer HE, Christopherson K, Hangoc G, Cooper S, Mantel C. 288.  et al. 2012. CD1d expression on and regulation of murine hematopoietic stem and progenitor cells. Blood 119:5731–41 [Google Scholar]
  289. Kotsianidis I, Silk JD, Spanoudakis E, Patterson S, Almeida A. 289.  et al. 2006. Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells. Blood 107:3138–44 [Google Scholar]
  290. De Santo C, Arscott R, Booth S, Karydis I, Jones M. 290.  et al. 2010. Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat. Immunol. 11:1039–46 [Google Scholar]
  291. Michel ML, Keller AC, Paget C, Fujio M, Trottein F. 291.  et al. 2007. Identification of an IL-17-producing NK1.1neg iNKT cell population involved in airway neutrophilia. J. Exp. Med. 204:995–1001 [Google Scholar]
  292. Pichavant M, Goya S, Meyer EH, Johnston RA, Kim HY. 292.  et al. 2008. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J. Exp. Med. 205:385–93 [Google Scholar]
  293. Wingender G, Hiss M, Engel I, Peukert K, Ley K. 293.  et al. 2012. Neutrophilic granulocytes modulate invariant NKT cell function in mice and humans. J. Immunol. 188:3000–8 [Google Scholar]
  294. Diana J, Griseri T, Lagaye S, Beaudoin L, Autrusseau E. 294.  et al. 2009. NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner. Immunity 30:289–99 [Google Scholar]
  295. Diana J, Brezar V, Beaudoin L, Dalod M, Mellor A. 295.  et al. 2011. Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay. J. Exp. Med. 208:729–45 [Google Scholar]
  296. Shimizu K, Asakura M, Shinga J, Sato Y, Kitahara S. 296.  et al. 2013. Invariant NKT cells induce plasmacytoid dendritic cell (DC) cross-talk with conventional DCs for efficient memory CD8+ T cell induction. J. Immunol. 190:5609–19 [Google Scholar]
  297. Marschner A, Rothenfusser S, Hornung V, Prell D, Krug A. 297.  et al. 2005. CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells. Eur. J. Immunol. 35:2347–57 [Google Scholar]
  298. Montoya CJ, Jie HB, Al-Harthi L, Mulder C, Patino PJ. 298.  et al. 2006. Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells. J. Immunol. 177:1028–39 [Google Scholar]
  299. Parekh VV, Wilson MT, Olivares-Villagomez D, Singh AK, Wu L. 299.  et al. 2005. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Investig. 115:2572–83 [Google Scholar]
  300. Kmieciak M, Basu D, Payne KK, Toor A, Yacoub A. 300.  et al. 2011. Activated NKT cells and NK cells render T cells resistant to myeloid-derived suppressor cells and result in an effective adoptive cellular therapy against breast cancer in the FVBN202 transgenic mouse. J. Immunol. 187:708–17 [Google Scholar]
  301. Lee JM, Seo JH, Kim YJ, Kim YS, Ko HJ, Kang CY. 301.  2012. The restoration of myeloid-derived suppressor cells as functional antigen-presenting cells by NKT cell help and all-trans-retinoic acid treatment. Int. J. Cancer 131:741–51 [Google Scholar]
  302. Ko HJ, Lee JM, Kim YJ, Kim YS, Lee KA, Kang CY. 302.  2009. Immunosuppressive myeloid-derived suppressor cells can be converted into immunogenic APCs with the help of activated NKT cells: an alternative cell-based antitumor vaccine. J. Immunol. 182:1818–28 [Google Scholar]
  303. Wu L, Van Kaer L. 303.  2011. Natural killer T cells in health and disease. Front. Biosci. 3:236–51 [Google Scholar]
  304. Stober D, Jomantaite I, Schirmbeck R, Reimann J. 304.  2003. NKT cells provide help for dendritic cell-dependent priming of MHC class I-restricted CD8+ T cells in vivo. J. Immunol. 170:2540–48 [Google Scholar]
  305. Gonzalez-Aseguinolaza G, Van Kaer L, Bergmann CC, Wilson JM, Schmieg J. 305.  et al. 2002. Natural killer T cell ligand α-galactosylceramide enhances protective immunity induced by malaria vaccines. J. Exp. Med. 195:617–24 [Google Scholar]
  306. Ko SY, Ko HJ, Chang WS, Park SH, Kweon MN, Kang CY. 306.  2005. α-Galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor. J. Immunol. 175:3309–17 [Google Scholar]
  307. Ko SY, Lee KA, Youn HJ, Kim YJ, Ko HJ. 307.  et al. 2007. Mediastinal lymph node CD8α DC initiate antigen presentation following intranasal coadministration of α-GalCer. Eur. J. Immunol. 37:2127–37 [Google Scholar]
  308. Liu K, Idoyaga J, Charalambous A, Fujii S, Bonito A. 308.  et al. 2005. Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells. J. Exp. Med. 202:1507–16 [Google Scholar]
  309. Youn HJ, Ko SY, Lee KA, Ko HJ, Lee YS. 309.  et al. 2007. A single intranasal immunization with inactivated influenza virus and α-galactosylceramide induces long-term protective immunity without redirecting antigen to the central nervous system. Vaccine 25:5189–98 [Google Scholar]
  310. Hermans IF, Silk JD, Gileadi U, Masri SH, Shepherd D. 310.  et al. 2007. Dendritic cell function can be modulated through cooperative actions of TLR ligands and invariant NKT cells. J. Immunol. 178:2721–29 [Google Scholar]
  311. Kim D, Hung CF, Wu TC, Park YM. 311.  2010. DNA vaccine with α-galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells. Vaccine 28:7297–305 [Google Scholar]
  312. Huang Y, Chen A, Li X, Chen Z, Zhang W. 312.  et al. 2008. Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, α-galactosylceramide. Vaccine 26:1807–16 [Google Scholar]
  313. Dondji B, Deak E, Goldsmith-Pestana K, Perez-Jimenez E, Esteban M. 313.  et al. 2008. Intradermal NKT cell activation during DNA priming in heterologous prime-boost vaccination enhances T cell responses and protection against Leishmania. Eur. J. Immunol. 38:706–19 [Google Scholar]
  314. Fernandez CS, Cameron G, Godfrey DI, Kent SJ. 314.  2012. Ex-vivo α-galactosylceramide activation of NKT cells in humans and macaques. J. Immunol. Methods 382:150–59 [Google Scholar]
  315. Fernandez CS, Jegaskanda S, Godfrey DI, Kent SJ. 315.  2013. In-vivo stimulation of macaque natural killer T cells with α-galactosylceramide. Clin. Exp. Immunol. 173:480–92 [Google Scholar]
  316. Wen X, Rao P, Carreno LJ, Kim S, Lawrenczyk A. 316.  et al. 2013. Human CD1d knock-in mouse model demonstrates potent antitumor potential of human CD1d-restricted invariant natural killer T cells. Proc. Natl. Acad. Sci. USA 110:2963–68 [Google Scholar]
  317. Lockridge JL, Chen X, Zhou Y, Rajesh D, Roenneburg DA. 317.  et al. 2011. Analysis of the CD1 antigen presenting system in humanized SCID mice. PLoS ONE 6:e21701 [Google Scholar]
  318. Silk J, Salio M, Reddy BG, Shepherd D, Gileadi U. 318.  et al. 2008. Non-glycosidic CD1d lipid ligands activate human and murine invariant NKT cells. J. Immunol. 180:11 [Google Scholar]
  319. Wojno J, Jukes JP, Ghadbane H, Shepherd D, Besra GS. 319.  et al. 2012. Amide analogues of CD1d agonists modulate iNKT-cell-mediated cytokine production. ACS Chem. Biol. 7:847–55 [Google Scholar]
  320. Jervis PJ, Polzella P, Wojno J, Jukes JP, Ghadbane H. 320.  et al. 2013. Design, synthesis, and functional activity of labeled CD1d glycolipid agonists. Bioconjug. Chem. 24:586–94 [Google Scholar]
  321. Hogan AE, O'Reilly V, Dunne MR, Dere RT, Zeng SG. 321.  et al. 2011. Activation of human invariant natural killer T cells with a thioglycoside analogue of α-galactosylceramide. Clin. Immunol. 140:196–207 [Google Scholar]
  322. Padte NN, Li X, Tsuji M, Vasan S. 322.  2011. Clinical development of a novel CD1d-binding NKT cell ligand as a vaccine adjuvant. Clin. Immunol. 140:142–51 [Google Scholar]
  323. Bol KF, Tel J, de Vries IJ, Figdor CG. 323.  2013. Naturally circulating dendritic cells to vaccinate cancer patients. Oncoimmunology 2:e23431 [Google Scholar]
  324. Zeng J, Shahbazi M, Wu C, Toh HC, Wang S. 324.  2012. Enhancing immunostimulatory function of human embryonic stem cell-derived dendritic cells by CD1d overexpression. J. Immunol. 188:4297–304 [Google Scholar]
  325. Silk KM, Silk JD, Ichiryu N, Davies TJ, Nolan KF. 325.  et al. 2012. Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141+XCR1+ dendritic cells. Gene Ther. 19:1035–40 [Google Scholar]
  326. Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. 326.  2013. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J. Exp. Med. 210:1389–402 [Google Scholar]
  327. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA. 327.  et al. 2013. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med 369:122–33 [Google Scholar]
  328. Petersen TR, Sika-Paotonu D, Knight DA, Dickgreber N, Farrand KJ. 328.  et al. 2010. Potent anti-tumor responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand. Immunol. Cell Biol. 88:596–604 [Google Scholar]
  329. Mattarollo SR, Steegh K, Li M, Duret H, Foong Ngiow S, Smyth MJ. 329.  2013. Transient Foxp3+ regulatory T-cell depletion enhances therapeutic anticancer vaccination targeting the immune-stimulatory properties of NKT cells. Immunol. Cell Biol. 91:105–14 [Google Scholar]
  330. Parekh VV, Lalani S, Kim S, Halder R, Azuma M. 330.  et al. 2009. PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J. Immunol. 182:2816–26 [Google Scholar]
  331. Shamshiev A, Gober HJ, Donda A, Mazorra Z, Mori L, De Libero G. 331.  2002. Presentation of the same glycolipid by different CD1 molecules. J. Exp. Med. 195:1013–21 [Google Scholar]
  332. Moody DB, Young DC, Cheng TY, Rosat JP, Roura-Mir C. 332.  et al. 2004. T cell activation by lipopeptide antigens. Science 303:527–31 [Google Scholar]
  333. Rosat JP, Grant EP, Beckman EM, Dascher CC, Sieling PA. 333.  et al. 1999. CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ αβ T cell pool. J. Immunol. 162:366–71 [Google Scholar]
  334. Kasmar AG, Van Rhijn I, Magalhaes KG, Young DC, Cheng TY. 334.  et al. 2013. Cutting edge: CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo. J. Immunol. 191:4499–503 [Google Scholar]
  335. de Jong A, Pena-Cruz V, Cheng TY, Clark RA, Van Rhijn I, Moody DB. 335.  2010. CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire. Nat. Immunol. 11:1102–9 [Google Scholar]
  336. de Lalla C, Lepore M, Piccolo FM, Rinaldi A, Scelfo A. 336.  et al. 2011. High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells. Eur. J. Immunol. 41:602–10 [Google Scholar]
  337. Seshadri C, Shenoy M, Wells RD, Hensley-McBain T, Andersen-Nissen E. 337.  et al. 2013. Human CD1a deficiency is common and genetically regulated. J. Immunol. 191:1586–93 [Google Scholar]
  338. Shamshiev A, Donda A, Carena I, Mori L, Kappos L, De Libero G. 338.  1999. Self glycolipids as T-cell autoantigens. Eur. J. Immunol. 29:1667–75 [Google Scholar]
  339. Moody DB, Besra GS, Wilson IA, Porcelli SA. 339.  1999. The molecular basis of CD1-mediated presentation of lipid antigens. Immunol. Rev. 172:285–96 [Google Scholar]
  340. Sieling PA, Chatterjee D, Porcelli SA, Prigozy TI, Mazzaccaro RJ. 340.  et al. 1995. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269:227–30 [Google Scholar]
  341. Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB. 341.  1994. Recognition of a lipid antigen by CD1-restricted αβ+ T cells. Nature 372:691–94 [Google Scholar]
  342. Moody DB, Reinhold BB, Guy MR, Beckman EM, Frederique DE. 342.  et al. 1997. Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science 278:283–86 [Google Scholar]
  343. Porcelli S, Morita CT, Brenner MB. 343.  1992. CD1b restricts the response of human CD48 T lymphocytes to a microbial antigen. Nature 360:593–97 [Google Scholar]
  344. Kasmar AG, van Rhijn I, Cheng TY, Turner M, Seshadri C. 344.  et al. 2011. CD1b tetramers bind αβ T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans. J. Exp. Med. 208:1741–47 [Google Scholar]
  345. Ly D, Kasmar AG, Cheng TY, de Jong A, Huang S. 345.  et al. 2013. CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. J. Exp. Med. 210:729–41 [Google Scholar]
  346. Gilleron M, Stenger S, Mazorra Z, Wittke F, Mariotti S. 346.  et al. 2004. Diacylated sulfoglycolipids are novel mycobacterial antigens stimulating CD1-restricted T cells during infection with Mycobacterium tuberculosis. J. Exp. Med. 199:649–59 [Google Scholar]
  347. Montamat-Sicotte DJ, Millington KA, Willcox CR, Hingley-Wilson S, Hackforth S. 347.  et al. 2011. A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection. J. Clin. Investig. 121:2493–503 [Google Scholar]
  348. Hiromatsu K, Dascher CC, LeClair KP, Sugita M, Furlong ST. 348.  et al. 2002. Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. J. Immunol. 169:330–39 [Google Scholar]
  349. Hiromatsu K, Dascher CC, Sugita M, Gingrich-Baker C, Behar SM. 349.  et al. 2002. Characterization of guinea-pig group 1 CD1 proteins. Immunology 106:159–72 [Google Scholar]
  350. Felio K, Nguyen H, Dascher CC, Choi HJ, Li S. 350.  et al. 2009. CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice. J. Exp. Med. 206:2497–509 [Google Scholar]
  351. Matsunaga I, Bhatt A, Young DC, Cheng TY, Eyles SJ. 351.  et al. 2004. Mycobacterium tuberculosis pks12 produces a novel polyketide presented by CD1c to T cells. J. Exp. Med. 200:1559–69 [Google Scholar]
  352. Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS. 352.  et al. 2000. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 404:884–88 [Google Scholar]
  353. de Jong A, Arce EC, Cheng TY, van Summeren RP, Feringa BL. 353.  et al. 2007. CD1c presentation of synthetic glycolipid antigens with foreign alkyl branching motifs. Chem. Biol. 14:1232–42 [Google Scholar]
  354. Van Rhijn I, Young DC, De Jong A, Vazquez J, Cheng TY. 354.  et al. 2009. CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids. J. Exp. Med. 206:1409–22 [Google Scholar]
  355. Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM. 355.  et al. 2010. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol. 8:e1000407 [Google Scholar]
  356. Le Bourhis L, Martin E, Peguillet I, Guihot A, Froux N. 356.  et al. 2010. Antimicrobial activity of mucosal-associated invariant T cells. Nat. Immunol. 11:701–8 [Google Scholar]
  357. Dusseaux M, Martin E, Serriari N, Peguillet I, Premel V. 357.  et al. 2011. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117:1250–59 [Google Scholar]
  358. Reantragoon R, Kjer-Nielsen L, Patel O, Chen Z, Illing PT. 358.  et al. 2012. Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor. J. Exp. Med. 209:761–74 [Google Scholar]
  359. Tilloy F, Treiner E, Park SH, Garcia C, Lemonnier F. 359.  et al. 1999. An invariant T cell receptor α chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted α/β T cell subpopulation in mammals. J. Exp. Med. 189:1907–21 [Google Scholar]
  360. Martin E, Treiner E, Duban L, Guerri L, Laude H. 360.  et al. 2009. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 7:e54 [Google Scholar]
  361. Seach N, Guerri L, Le Bourhis L, Mburu Y, Cui Y. 361.  et al. 2013. Double positive thymocytes select mucosal-associated invariant T cells. J. Immunol. 191:6002–9 [Google Scholar]
  362. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V. 362.  et al. 2003. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164–69 [Google Scholar]
  363. Walker LJ, Kang YH, Smith MO, Tharmalingham H, Ramamurthy N. 363.  et al. 2012. Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells. Blood 119:422–33 [Google Scholar]
  364. Tang XZ, Jo J, Tan AT, Sandalova E, Chia A. 364.  et al. 2013. IL-7 licenses activation of human liver intrasinusoidal mucosal-associated invariant T cells. J. Immunol. 190:3142–52 [Google Scholar]
  365. Georgel P, Radosavljevic M, Macquin C, Bahram S. 365.  2011. The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol. Immunol. 48:769–75 [Google Scholar]
  366. Chua WJ, Truscott SM, Eickhoff CS, Blazevic A, Hoft DF, Hansen TH. 366.  2012. Polyclonal mucosa-associated invariant T cells have unique innate functions in bacterial infection. Infect. Immun. 80:3256–67 [Google Scholar]
  367. Riegert P, Wanner V, Bahram S. 367.  1998. Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene. J. Immunol. 161:4066–77 [Google Scholar]
  368. Huang S, Gilfillan S, Cella M, Miley MJ, Lantz O. 368.  et al. 2005. Evidence for MR1 antigen presentation to mucosal-associated invariant T cells. J. Biol. Chem. 280:21183–93 [Google Scholar]
  369. Huang S, Gilfillan S, Kim S, Thompson B, Wang X. 369.  et al. 2008. MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells. J. Exp. Med. 205:1201–11 [Google Scholar]
  370. Huang S, Martin E, Kim S, Yu L, Soudais C. 370.  et al. 2009. MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proc. Natl. Acad. Sci. USA 106:8290–95 [Google Scholar]
  371. Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB. 371.  et al. 2013. Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J. Exp. Med. 210:2305–20 [Google Scholar]
/content/journals/10.1146/annurev-immunol-032713-120243
Loading
/content/journals/10.1146/annurev-immunol-032713-120243
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article