Advertisement

Cellular and Molecular Life Sciences

, Volume 75, Issue 9, pp 1623–1639 | Cite as

Molecular recognition of microbial lipid-based antigens by T cells

  • Stephanie Gras
  • Ildiko Van Rhijn
  • Adam Shahine
  • Jérôme Le Nours
Review
  • 281 Downloads

Abstract

The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation. Over the past decades, numerous CD1-presented self- and bacterial lipid-based antigens have been isolated and characterized. However, our understanding at the molecular level of T cell immunity to CD1 molecules presenting microbial lipid-based antigens is still largely unexplored. Here, we review the insights and the molecular basis underpinning the recognition of microbial lipid-based antigens by T cells.

Keywords

T cells CD1-mediated immunity Microbial lipids Antigens T cell receptors Molecular recognition 

Notes

Acknowledgements

Our research is supported by the US National Institutes of Health (NIH) (AI 111224), Monash University (Australia), the Australian National Health and Medical Research (NHMRC), and the Australian Research Council (ARC). SG is a Monash Senior Research Fellow and J. L. N. is an ARC Future Fellow (FT160100074).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

References

  1. 1.
    Miles JJ, McCluskey J, Rossjohn J, Gras S (2015) Understanding the complexity and malleability of T-cell recognition. Immunol Cell Biol 93(5):433–441.  https://doi.org/10.1038/icb.2014.112 PubMedCrossRefGoogle Scholar
  2. 2.
    Rossjohn J, Gras S, Miles JJ, Turner SJ, Godfrey DI, McCluskey J (2015) T cell antigen receptor recognition of antigen-presenting molecules. Annu Rev Immunol 33:169–200.  https://doi.org/10.1146/annurev-immunol-032414-112334 PubMedCrossRefGoogle Scholar
  3. 3.
    Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB (1994) Recognition of a lipid antigen by CD1-restricted alpha beta + T cells. Nature 372(6507):691–694.  https://doi.org/10.1038/372691a0 PubMedCrossRefGoogle Scholar
  4. 4.
    Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O’Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491(7426):717–723.  https://doi.org/10.1038/nature11605 PubMedCrossRefGoogle Scholar
  5. 5.
    Patel O, Kjer-Nielsen L, Le Nours J, Eckle SB, Birkinshaw R, Beddoe T, Corbett AJ, Liu L, Miles JJ, Meehan B, Reantragoon R, Sandoval-Romero ML, Sullivan LC, Brooks AG, Chen Z, Fairlie DP, McCluskey J, Rossjohn J (2013) Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Nature Commun 4:2142.  https://doi.org/10.1038/ncomms3142 CrossRefGoogle Scholar
  6. 6.
    Adams EJ, Luoma AM (2013) The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I-like molecules. Annu Rev Immunol 31:529–561.  https://doi.org/10.1146/annurev-immunol-032712-095912 PubMedCrossRefGoogle Scholar
  7. 7.
    Van Rhijn I, Godfrey DI, Rossjohn J, Moody DB (2015) Lipid and small-molecule display by CD1 and MR1. Nat Rev Immunol 15(10):643–654.  https://doi.org/10.1038/nri3889 PubMedCrossRefGoogle Scholar
  8. 8.
    Zajonc DM, Flajnik MF (2016) CD1, MR1, NKT, and MAIT: evolution and origins of non-peptidic antigen recognition by T lymphocytes. Immunogenetics 68(8):489–490.  https://doi.org/10.1007/s00251-016-0941-y PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Godfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB (2015) The burgeoning family of unconventional T cells. Nat Immunol 16(11):1114–1123.  https://doi.org/10.1038/ni.3298 PubMedCrossRefGoogle Scholar
  10. 10.
    Garcia-Alles LF, Giacometti G, Versluis C, Maveyraud L, de Paepe D, Guiard J, Tranier S, Gilleron M, Prandi J, Hanau D, Heck AJ, Mori L, De Libero G, Puzo G, Mourey L, de la Salle H (2011) Crystal structure of human CD1e reveals a groove suited for lipid-exchange processes. Proc Natl Acad Sci USA 108(32):13230–13235.  https://doi.org/10.1073/pnas.1105627108 PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Zajonc DM (2016) The CD1 family: serving lipid antigens to T cells since the Mesozoic era. Immunogenetics 68(8):561–576.  https://doi.org/10.1007/s00251-016-0931-0 PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Moody DB, Zajonc DM, Wilson IA (2005) Anatomy of CD1-lipid antigen complexes. Nat Rev Immunol 5(5):387–399.  https://doi.org/10.1038/nri1605 PubMedCrossRefGoogle Scholar
  13. 13.
    Smith ME, Thomas JA, Bodmer WF (1988) CD1c antigens are present in normal and neoplastic B-cells. J Pathol 156(2):169–177.  https://doi.org/10.1002/path.1711560212 PubMedCrossRefGoogle Scholar
  14. 14.
    Pena-Cruz V, Ito S, Oukka M, Yoneda K, Dascher CC, Von Lichtenberg F, Sugita M (2001) Extraction of human Langerhans cells: a method for isolation of epidermis-resident dendritic cells. J Immunol Methods 255(1–2):83–91PubMedCrossRefGoogle Scholar
  15. 15.
    Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360(6401):258–261.  https://doi.org/10.1038/360258a0 PubMedCrossRefGoogle Scholar
  16. 16.
    de Jong A, Cheng TY, Huang S, Gras S, Birkinshaw RW, Kasmar AG, Van Rhijn I, Pena-Cruz V, Ruan DT, Altman JD, Rossjohn J, Moody DB (2014) CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens. Nat Immunol 15(2):177–185.  https://doi.org/10.1038/ni.2790 PubMedCrossRefGoogle Scholar
  17. 17.
    de Jong A, Pena-Cruz V, Cheng TY, Clark RA, Van Rhijn I, Moody DB (2010) CD1a-autoreactive T cells are a normal component of the human alphabeta T cell repertoire. Nat Immunol 11(12):1102–1109.  https://doi.org/10.1038/ni.1956 PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Ly D, Moody DB (2014) The CD1 size problem: lipid antigens, ligands, and scaffolds. Cell Mol Life Sci CMLS 71(16):3069–3079.  https://doi.org/10.1007/s00018-014-1603-6 PubMedCrossRefGoogle Scholar
  19. 19.
    Skold M, Behar SM (2003) Role of CD1d-restricted NKT cells in microbial immunity. Infect Immun 71(10):5447–5455PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Godfrey DI, McCluskey J, Rossjohn J (2005) CD1d antigen presentation: treats for NKT cells. Nat Immunol 6(8):754–756.  https://doi.org/10.1038/ni0805-754 PubMedCrossRefGoogle Scholar
  21. 21.
    Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L (2004) NKT cells: what’s in a name? Nat Rev Immunol 4(3):231–237.  https://doi.org/10.1038/nri1309 PubMedCrossRefGoogle Scholar
  22. 22.
    Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Koseki H, Taniguchi M (1997) CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278(5343):1626–1629PubMedCrossRefGoogle Scholar
  23. 23.
    Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI (2012) Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev Immunol 12(12):845–857.  https://doi.org/10.1038/nri3328 PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Patel O, Pellicci DG, Gras S, Sandoval-Romero ML, Uldrich AP, Mallevaey T, Clarke AJ, Le Nours J, Theodossis A, Cardell SL, Gapin L, Godfrey DI, Rossjohn J (2012) Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat Immunol 13(9):857–863.  https://doi.org/10.1038/ni.2372 PubMedCrossRefGoogle Scholar
  25. 25.
    Girardi E, Maricic I, Wang J, Mac TT, Iyer P, Kumar V, Zajonc DM (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(9):851–856.  https://doi.org/10.1038/ni.2371 PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Brigl M, Brenner MB (2004) CD1: antigen presentation and T cell function. Annu Rev Immunol 22:817–890.  https://doi.org/10.1146/annurev.immunol.22.012703.104608 PubMedCrossRefGoogle Scholar
  27. 27.
    Uldrich AP, Patel O, Cameron G, Pellicci DG, Day EB, Sullivan LC, Kyparissoudis K, Kjer-Nielsen L, Vivian JP, Cao B, Brooks AG, Williams SJ, Illarionov P, Besra GS, Turner SJ, Porcelli SA, McCluskey J, Smyth MJ, Rossjohn J, Godfrey DI (2011) A semi-invariant Valpha10 + T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. Nat Immunol 12(7):616–623.  https://doi.org/10.1038/ni.2051 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Pellicci DG, Uldrich AP, Le Nours J, Ross F, Chabrol E, Eckle SB, de Boer R, Lim RT, McPherson K, Besra G, Howell AR, Moretta L, McCluskey J, Heemskerk MH, Gras S, Rossjohn J, Godfrey DI (2014) The molecular bases of delta/alphabeta T cell-mediated antigen recognition. J Exp Med 211(13):2599–2615.  https://doi.org/10.1084/jem.20141764 PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Zajonc DM, Girardi E (2014) A gammadelta T-cell glimpse of glycolipids. Immunol Cell Biol 92(2):99–100.  https://doi.org/10.1038/icb.2013.83 PubMedCrossRefGoogle Scholar
  30. 30.
    Uldrich AP, Le Nours J, Pellicci DG, Gherardin NA, McPherson KG, Lim RT, Patel O, Beddoe T, Gras S, Rossjohn J, Godfrey DI (2013) CD1d-lipid antigen recognition by the gammadelta TCR. Nat Immunol 14(11):1137–1145.  https://doi.org/10.1038/ni.2713 PubMedCrossRefGoogle Scholar
  31. 31.
    Luoma AM, Castro CD, Mayassi T, Bembinster LA, Bai L, Picard D, Anderson B, Scharf L, Kung JE, Sibener LV, Savage PB, Jabri B, Bendelac A, Adams EJ (2013) Crystal structure of Vdelta1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human gammadelta T cells. Immunity 39(6):1032–1042.  https://doi.org/10.1016/j.immuni.2013.11.001 PubMedCrossRefGoogle Scholar
  32. 32.
    Koch M, Stronge VS, Shepherd D, Gadola SD, Mathew B, Ritter G, Fersht AR, Besra GS, Schmidt RR, Jones EY, Cerundolo V (2005) The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat Immunol 6(8):819–826.  https://doi.org/10.1038/ni1225 PubMedCrossRefGoogle Scholar
  33. 33.
    Zeng Z, Castano AR, Segelke BW, Stura EA, Peterson PA, Wilson IA (1997) Crystal structure of mouse CD1: an MHC-like fold with a large hydrophobic binding groove. Science 277(5324):339–345PubMedCrossRefGoogle Scholar
  34. 34.
    Kinjo Y, Ueno K (2011) iNKT cells in microbial immunity: recognition of microbial glycolipids. Microbiol Immunol 55(7):472–482.  https://doi.org/10.1111/j.1348-0421.2011.00338.x PubMedCrossRefGoogle Scholar
  35. 35.
    Zajonc DM, Girardi E (2015) Recognition of microbial glycolipids by natural killer T cells. Front Immunol 6:400.  https://doi.org/10.3389/fimmu.2015.00400 PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Van Kaer L, Parekh VV, Wu L (2015) The response of CD1d-restricted invariant NKT cells to microbial pathogens and their products. Front Immunol 6:226.  https://doi.org/10.3389/fimmu.2015.00226 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Fischer K, Scotet E, Niemeyer M, Koebernick H, Zerrahn J, Maillet S, Hurwitz R, Kursar M, Bonneville M, Kaufmann SH, Schaible UE (2004) Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc Natl Acad Sci USA 101(29):10685–10690.  https://doi.org/10.1073/pnas.0403787101 PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Venkataswamy MM, Porcelli SA (2010) Lipid and glycolipid antigens of CD1d-restricted natural killer T cells. Semin Immunol 22(2):68–78.  https://doi.org/10.1016/j.smim.2009.10.003 PubMedCrossRefGoogle Scholar
  39. 39.
    Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, Zajonc DM, Ben-Menachem G, Ainge GD, Painter GF, Khurana A, Hoebe K, Behar SM, Beutler B, Wilson IA, Tsuji M, Sellati TJ, Wong CH, Kronenberg M (2006) Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7(9):978–986.  https://doi.org/10.1038/ni1380 PubMedCrossRefGoogle Scholar
  40. 40.
    An D, Oh SF, Olszak T, Neves JF, Avci FY, Erturk-Hasdemir D, Lu X, Zeissig S, Blumberg RS, Kasper DL (2014) Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156(1–2):123–133.  https://doi.org/10.1016/j.cell.2013.11.042 PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Wieland Brown LC, Penaranda C, Kashyap PC, Williams BB, Clardy J, Kronenberg M, Sonnenburg JL, Comstock LE, Bluestone JA, Fischbach MA (2013) Production of alpha-galactosylceramide by a prominent member of the human gut microbiota. PLoS Biol 11(7):e1001610.  https://doi.org/10.1371/journal.pbio.1001610 PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Walker D, Beutler B, Teyton L, Savage PB, Bendelac A (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434(7032):525–529.  https://doi.org/10.1038/nature03408 PubMedCrossRefGoogle Scholar
  43. 43.
    Kinjo Y, Wu D, Kim G, Xing GW, Poles MA, Ho DD, Tsuji M, Kawahara K, Wong CH, Kronenberg M (2005) Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434(7032):520–525.  https://doi.org/10.1038/nature03407 PubMedCrossRefGoogle Scholar
  44. 44.
    Kawahara K, Moll H, Knirel YA, Seydel U, Zahringer U (2000) Structural analysis of two glycosphingolipids from the lipopolysaccharide-lacking bacterium Sphingomonas capsulata. Eur J Biochem/FEBS 267(6):1837–1846CrossRefGoogle Scholar
  45. 45.
    Florence WC, Bhat RK, Joyce S (2008) CD1d-restricted glycolipid antigens: presentation principles, recognition logic and functional consequences. Expert Rev Mol Med 10:e20.  https://doi.org/10.1017/S1462399408000732 PubMedCrossRefGoogle Scholar
  46. 46.
    Borg NA, Wun KS, Kjer-Nielsen L, Wilce MC, Pellicci DG, Koh R, Besra GS, Bharadwaj M, Godfrey DI, McCluskey J, Rossjohn J (2007) CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448(7149):44–49.  https://doi.org/10.1038/nature05907 PubMedCrossRefGoogle Scholar
  47. 47.
    Pellicci DG, Patel O, Kjer-Nielsen L, Pang SS, Sullivan LC, Kyparissoudis K, Brooks AG, Reid HH, Gras S, Lucet IS, Koh R, Smyth MJ, Mallevaey T, Matsuda JL, Gapin L, McCluskey J, Godfrey DI, Rossjohn J (2009) Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors. Immunity 31(1):47–59.  https://doi.org/10.1016/j.immuni.2009.04.018 PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Wu D, Zajonc DM, Fujio M, Sullivan BA, Kinjo Y, Kronenberg M, Wilson IA, Wong CH (2006) Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d. Proc Natl Acad Sci USA 103(11):3972–3977.  https://doi.org/10.1073/pnas.0600285103 PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Olson CM Jr, Bates TC, Izadi H, Radolf JD, Huber SA, Boyson JE, Anguita J (2009) Local production of IFN-gamma by invariant NKT cells modulates acute Lyme carditis. J Immunol 182(6):3728–3734.  https://doi.org/10.4049/jimmunol.0804111 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Wang J, Li Y, Kinjo Y, Mac TT, Gibson D, Painter GF, Kronenberg M, Zajonc DM (2010) Lipid binding orientation within CD1d affects recognition of Borrelia burgdorferi antigens by NKT cells. Proc Natl Acad Sci USA 107(4):1535–1540.  https://doi.org/10.1073/pnas.0909479107 PubMedCrossRefGoogle Scholar
  51. 51.
    Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E, Li X, Li Y, Imamura M, Kaneko Y, Okawara A, Miyazaki Y, Gomez-Velasco A, Rogers P, Dahesh S, Uchiyama S, Khurana A, Kawahara K, Yesilkaya H, Andrew PW, Wong CH, Kawakami K, Nizet V, Besra GS, Tsuji M, Zajonc DM, Kronenberg M (2011) Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. Nat Immunol 12(10):966–974.  https://doi.org/10.1038/ni.2096 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Mallevaey T, Clarke AJ, Scott-Browne JP, Young MH, Roisman LC, Pellicci DG, Patel O, Vivian JP, Matsuda JL, McCluskey J, Godfrey DI, Marrack P, Rossjohn J, Gapin L (2011) A molecular basis for NKT cell recognition of CD1d-self-antigen. Immunity 34(3):315–326.  https://doi.org/10.1016/j.immuni.2011.01.013 PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Zajonc DM, Ainge GD, Painter GF, Severn WB, Wilson IA (2006) Structural characterization of mycobacterial phosphatidylinositol mannoside binding to mouse CD1d. J Immunol 177(7):4577–4583PubMedCrossRefGoogle Scholar
  54. 54.
    Giabbai B, Sidobre S, Crispin MD, Sanchez-Ruiz Y, Bachi A, Kronenberg M, Wilson IA, Degano M (2005) Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation. J Immunol 175(2):977–984PubMedCrossRefGoogle Scholar
  55. 55.
    Lotter H, Gonzalez-Roldan N, Lindner B, Winau F, Isibasi A, Moreno-Lafont M, Ulmer AJ, Holst O, Tannich E, Jacobs T (2009) Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathog 5(5):e1000434.  https://doi.org/10.1371/journal.ppat.1000434 PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Hirai Y, Haque M, Yoshida T, Yokota K, Yasuda T, Oguma K (1995) Unique cholesteryl glucosides in Helicobacter pylori: composition and structural analysis. J Bacteriol 177(18):5327–5333PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Ito Y, Vela JL, Matsumura F, Hoshino H, Tyznik A, Lee H, Girardi E, Zajonc DM, Liddington R, Kobayashi M, Bao X, Bugaytsova J, Boren T, Jin R, Zong Y, Seeberger PH, Nakayama J, Kronenberg M, Fukuda M (2013) Helicobacter pylori cholesteryl alpha-glucosides contribute to its pathogenicity and immune response by natural killer T cells. PLoS One 8(12):e78191.  https://doi.org/10.1371/journal.pone.0078191 PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Chang YJ, Kim HY, Albacker LA, Lee HH, Baumgarth N, Akira S, Savage PB, Endo S, Yamamura T, Maaskant J, Kitano N, Singh A, Bhatt A, Besra GS, van den Elzen P, Appelmelk B, Franck RW, Chen G, DeKruyff RH, Shimamura M, Illarionov P, Umetsu DT (2011) Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J Clin Investig 121(1):57–69.  https://doi.org/10.1172/JCI44845 PubMedCrossRefGoogle Scholar
  59. 59.
    Tatituri RV, Watts GF, Bhowruth V, Barton N, Rothchild A, Hsu FF, Almeida CF, Cox LR, Eggeling L, Cardell S, Rossjohn J, Godfrey DI, Behar SM, Besra GS, Brenner MB, Brigl M (2013) Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci USA 110(5):1827–1832.  https://doi.org/10.1073/pnas.1220601110 PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Wolf BJ, Tatituri RV, Almeida CF, Le Nours J, Bhowruth V, Johnson D, Uldrich AP, Hsu FF, Brigl M, Besra GS, Rossjohn J, Godfrey DI, Brenner MB (2015) Identification of a potent microbial lipid antigen for diverse NKT cells. J Immunol 195(6):2540–2551.  https://doi.org/10.4049/jimmunol.1501019 PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Li Y, Girardi E, Wang J, Yu ED, Painter GF, Kronenberg M, Zajonc DM (2010) The Valpha14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode. J Exp Med 207(11):2383–2393.  https://doi.org/10.1084/jem.20101335 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Girardi E, Yu ED, Li Y, Tarumoto N, Pei B, Wang J, Illarionov P, Kinjo Y, Kronenberg M, Zajonc DM (2011) Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for NKT cells. PLoS Biol 9(11):e1001189.  https://doi.org/10.1371/journal.pbio.1001189 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Pellicci DG, Clarke AJ, Patel O, Mallevaey T, Beddoe T, Le Nours J, Uldrich AP, McCluskey J, Besra GS, Porcelli SA, Gapin L, Godfrey DI, Rossjohn J (2011) Recognition of beta-linked self glycolipids mediated by natural killer T cell antigen receptors. Nat Immunol 12(9):827–833.  https://doi.org/10.1038/ni.2076 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Girardi E, Zajonc DM (2012) Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells. Immunol Rev 250(1):167–179.  https://doi.org/10.1111/j.1600-065X.2012.01166.x PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    De Silva AD, Park JJ, Matsuki N, Stanic AK, Brutkiewicz RR, Medof ME, Joyce S (2002) Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum. J Immunol 168(2):723–733PubMedCrossRefGoogle Scholar
  66. 66.
    Garcia-Alles LF, Versluis K, Maveyraud L, Vallina AT, Sansano S, Bello NF, Gober HJ, Guillet V, de la Salle H, Puzo G, Mori L, Heck AJ, De Libero G, Mourey L (2006) Endogenous phosphatidylcholine and a long spacer ligand stabilize the lipid-binding groove of CD1b. EMBO J 25(15):3684–3692.  https://doi.org/10.1038/sj.emboj.7601244 PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Huang S, Cheng TY, Young DC, Layre E, Madigan CA, Shires J, Cerundolo V, Altman JD, Moody DB (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(48):19335–19340.  https://doi.org/10.1073/pnas.1112969108 PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Shamshiev A, Donda A, Prigozy TI, Mori L, Chigorno V, Benedict CA, Kappos L, Sonnino S, Kronenberg M, De Libero G (2000) The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity 13(2):255–264PubMedCrossRefGoogle Scholar
  69. 69.
    Moody DB, Briken V, Cheng TY, Roura-Mir C, Guy MR, Geho DH, Tykocinski ML, Besra GS, Porcelli SA (2002) Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation. Nat Immunol 3(5):435–442.  https://doi.org/10.1038/ni780 PubMedCrossRefGoogle Scholar
  70. 70.
    Manolova V, Kistowska M, Paoletti S, Baltariu GM, Bausinger H, Hanau D, Mori L, De Libero G (2006) Functional CD1a is stabilized by exogenous lipids. Eur J Immunol 36(5):1083–1092.  https://doi.org/10.1002/eji.200535544 PubMedCrossRefGoogle Scholar
  71. 71.
    Briken V, Jackman RM, Watts GF, Rogers RA, Porcelli SA (2000) Human CD1b and CD1c isoforms survey different intracellular compartments for the presentation of microbial lipid antigens. J Exp Med 192(2):281–288PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Sugita M, van Der WN, Rogers RA, Peters PJ, Brenner MB (2000) CD1c molecules broadly survey the endocytic system. Proc Natl Acad Sci USA 97(15):8445–8450PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Briken V, Jackman RM, Dasgupta S, Hoening S, Porcelli SA (2002) Intracellular trafficking pathway of newly synthesized CD1b molecules. EMBO J 21(4):825–834.  https://doi.org/10.1093/emboj/21.4.825 PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Moody DB, Porcelli SA (2003) Intracellular pathways of CD1 antigen presentation. Nat Rev Immunol 3(1):11–22PubMedCrossRefGoogle Scholar
  75. 75.
    Cheng TY, Relloso M, Van Rhijn I, Young DC, Besra GS, Briken V, Zajonc DM, Wilson IA, Porcelli S, Moody DB (2006) Role of lipid trimming and CD1 groove size in cellular antigen presentation. EMBO J 25(13):2989–2999.  https://doi.org/10.1038/sj.emboj.7601185 PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Ly D, Kasmar AG, Cheng TY, de Jong A, Huang S, Roy S, Bhatt A, van Summeren RP, Altman JD, Jacobs WR Jr, Adams EJ, Minnaard AJ, Porcelli SA, Moody DB (2013) CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. J Exp Med 210(4):729–741.  https://doi.org/10.1084/jem.20120624 PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA (2000) CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 404(6780):884–888PubMedCrossRefGoogle Scholar
  78. 78.
    de Jong A, Arce EC, Cheng TY, van Summeren RP, Feringa BL, Dudkin V, Crich D, Matsunaga I, Minnaard AJ, Moody DB (2007) CD1c presentation of synthetic glycolipid antigens with foreign alkyl branching motifs. Chem Biol 14(11):1232–1242.  https://doi.org/10.1016/j.chembiol.2007.09.010 PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    de la Salle H, Mariotti S, Angenieux C, Gilleron M, Garcia-Alles LF, Malm D, Berg T, Paoletti S, Maitre B, Mourey L, Salamero J, Cazenave JP, Hanau D, Mori L, Puzo G, De Libero G (2005) Assistance of microbial glycolipid antigen processing by CD1e. Science 310(5752):1321–1324.  https://doi.org/10.1126/science.1115301 PubMedCrossRefGoogle Scholar
  80. 80.
    Gilleron M, Lepore M, Layre E, Cala-De Paepe D, Mebarek N, Shayman JA, Canaan S, Mori L, Carriere F, Puzo G, De Libero G (2016) Lysosomal lipases PLRP2 and LPLA2 process mycobacterial multi-acylated lipids and generate T cell stimulatory antigens. Cell Chem Biol 23(9):1147–1156.  https://doi.org/10.1016/j.chembiol.2016.07.021 PubMedCrossRefGoogle Scholar
  81. 81.
    Prigozy TI, Naidenko O, Qasba P, Elewaut D, Brossay L, Khurana A, Natori T, Koezuka Y, Kulkarni A, Kronenberg M (2001) Glycolipid antigen processing for presentation by CD1d molecules. Science 291(5504):664–667.  https://doi.org/10.1126/science.291.5504.664 PubMedCrossRefGoogle Scholar
  82. 82.
    Relloso M, Cheng TY, Im JS, Parisini E, Roura-Mir C, DeBono C, Zajonc DM, Murga LF, Ondrechen MJ, Wilson IA, Porcelli SA, Moody DB (2008) pH-dependent interdomain tethers of CD1b regulate its antigen capture. Immunity 28(6):774–786.  https://doi.org/10.1016/j.immuni.2008.04.017 PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Brozovic S, Nagaishi T, Yoshida M, Betz S, Salas A, Chen D, Kaser A, Glickman J, Kuo T, Little A, Morrison J, Corazza N, Kim JY, Colgan SP, Young SG, Exley M, Blumberg RS (2004) CD1d function is regulated by microsomal triglyceride transfer protein. Nat Med 10(5):535–539.  https://doi.org/10.1038/nm1043 PubMedCrossRefGoogle Scholar
  84. 84.
    Zhou D, Cantu C 3rd, Sagiv Y, Schrantz N, Kulkarni AB, Qi X, Mahuran DJ, Morales CR, Grabowski GA, Benlagha K, Savage P, Bendelac A, Teyton L (2004) Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science 303(5657):523–527.  https://doi.org/10.1126/science.1092009 PubMedCrossRefGoogle Scholar
  85. 85.
    Yuan W, Qi X, Tsang P, Kang SJ, Illarionov PA, Besra GS, Gumperz J, Cresswell P (2007) Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules. Proc Natl Acad Sci USA 104(13):5551–5556.  https://doi.org/10.1073/pnas.0700617104 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA, Modlin RL, Porcelli SA, Brinkmann V, Sugita M, Sandhoff K, Kaufmann SH, Schaible UE (2004) Saposin C is required for lipid presentation by human CD1b. Nat Immunol 5(2):169–174.  https://doi.org/10.1038/ni1035 PubMedCrossRefGoogle Scholar
  87. 87.
    Cala-De Paepe D, Layre E, Giacometti G, Garcia-Alles LF, Mori L, Hanau D, de Libero G, de la Salle H, Puzo G, Gilleron M (2012) Deciphering the role of CD1e protein in mycobacterial phosphatidyl-myo-inositol mannosides (PIM) processing for presentation by CD1b to T lymphocytes. J Biol Chem 287(37):31494–31502.  https://doi.org/10.1074/jbc.M112.386300 PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Grant EP, Degano M, Rosat JP, Stenger S, Modlin RL, Wilson IA, Porcelli SA, Brenner MB (1999) Molecular recognition of lipid antigens by T cell receptors. J Exp Med 189(1):195–205PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Van Rhijn I, Young DC, Im JS, Levery SB, Illarionov PA, Besra GS, Porcelli SA, Gumperz J, Cheng TY, Moody DB (2004) CD1d-restricted T cell activation by nonlipidic small molecules. Proc Natl Acad Sci USA 101(37):13578–13583.  https://doi.org/10.1073/pnas.0402838101 PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Van Rhijn I, Kasmar A, de Jong A, Gras S, Bhati M, Doorenspleet ME, de Vries N, Godfrey DI, Altman JD, de Jager W, Rossjohn J, Moody DB (2013) A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nat Immunol 14(7):706–713.  https://doi.org/10.1038/ni.2630 PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Van Rhijn I, Gherardin NA, Kasmar A, de Jager W, Pellicci DG, Kostenko L, Tan LL, Bhati M, Gras S, Godfrey DI, Rossjohn J, Moody DB (2014) TCR bias and affinity define two compartments of the CD1b-glycolipid-specific T cell repertoire. J Immunol 193(10):5338–5344.  https://doi.org/10.4049/jimmunol.1400158 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Turner SJ, Doherty PC, McCluskey J, Rossjohn J (2006) Structural determinants of T-cell receptor bias in immunity. Nat Rev Immunol 6(12):883–894.  https://doi.org/10.1038/nri1977 PubMedCrossRefGoogle Scholar
  93. 93.
    Spada FM, Grant EP, Peters PJ, Sugita M, Melian A, Leslie DS, Lee HK, van Donselaar E, Hanson DA, Krensky AM, Majdic O, Porcelli SA, Morita CT, Brenner MB (2000) Self-recognition of CD1 by gamma/delta T cells: implications for innate immunity. J Exp Med 191(6):937–948PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Russano AM, Bassotti G, Agea E, Bistoni O, Mazzocchi A, Morelli A, Porcelli SA, Spinozzi F (2007) CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta + T lymphocytes. J Immunol 178(6):3620–3626PubMedCrossRefGoogle Scholar
  95. 95.
    Roy S, Ly D, Castro CD, Li NS, Hawk AJ, Altman JD, Meredith SC, Piccirilli JA, Moody DB, Adams EJ (2016) Molecular analysis of lipid-reactive vdelta1 gammadelta T cells identified by CD1c tetramers. J Immunol 196(4):1933–1942.  https://doi.org/10.4049/jimmunol.1502202 PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Kasmar A, Van Rhijn I, Magalhaes KG, Young D, Cheng TY, Turner M, Schiefner A, Kalathur RC, Wilson A, Bhati M, Gras S, Rossjohn J, Shires J, Jakobsen S, Altman JD, Moody DB (2013) CD1a tetramers and dextramers identify human lipopeptide-specific T cells ex vivo. J Immunol 191:4499–4503PubMedCrossRefGoogle Scholar
  97. 97.
    Van Rhijn I, Iwany SK, Fodran P, Cheng TY, Gapin L, Minnaard AJ, Moody DB (2017) CD1b-mycolic acid tetramers demonstrate T-cell fine specificity for mycobacterial lipid tails. Eur J Immunol.  https://doi.org/10.1002/eji.201747062 PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Seshadri C, Lin L, Scriba TJ, Peterson G, Freidrich D, Frahm N, DeRosa SC, Moody DB, Prandi J, Gilleron M, Mahomed H, Jiang W, Finak G, Hanekom WA, Gottardo R, McElrath MJ, Hawn TR (2015) T cell responses against mycobacterial lipids and proteins are poorly correlated in South African adolescents. J Immunol 195(10):4595–4603.  https://doi.org/10.4049/jimmunol.1501285 PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Felio K, Nguyen H, Dascher CC, Choi HJ, Li S, Zimmer MI, Colmone A, Moody DB, Brenner MB, Wang CR (2009) CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice. J Exp Med 206(11):2497–2509.  https://doi.org/10.1084/jem.20090898 PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Dascher CC, Hiromatsu K, Xiong X, Morehouse C, Watts G, Liu G, McMurray DN, LeClair KP, Porcelli SA, Brenner MB (2003) Immunization with a mycobacterial lipid vaccine improves pulmonary pathology in the guinea pig model of tuberculosis. Int Immunol 15(8):915–925PubMedCrossRefGoogle Scholar
  101. 101.
    Porcelli S, Morita CT, Brenner MB (1992) CD1b restricts the response of human CD4-8-T lymphocytes to a microbial antigen. Nature 360(6404):593–597.  https://doi.org/10.1038/360593a0 PubMedCrossRefGoogle Scholar
  102. 102.
    Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA (2000) CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 404(6780):884–888.  https://doi.org/10.1038/35009119 PubMedCrossRefGoogle Scholar
  103. 103.
    Sieling PA, Chatterjee D, Porcelli SA, Prigozy TI, Mazzaccaro RJ, Soriano T, Bloom BR, Brenner MB, Kronenberg M, Brennan PJ et al (1995) CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269(5221):227–230PubMedCrossRefGoogle Scholar
  104. 104.
    Ernst WA, Maher J, Cho S, Niazi KR, Chatterjee D, Moody DB, Besra GS, Watanabe Y, Jensen PE, Porcelli SA, Kronenberg M, Modlin RL (1998) Molecular interaction of CD1b with lipoglycan antigens. Immunity 8(3):331–340PubMedCrossRefGoogle Scholar
  105. 105.
    Takayama K, Wang C, Besra GS (2005) Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18(1):81–101.  https://doi.org/10.1128/CMR.18.1.81-101.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Grant EP, Beckman EM, Behar SM, Degano M, Frederique D, Besra GS, Wilson IA, Porcelli SA, Furlong ST, Brenner MB (2002) Fine specificity of TCR complementarity-determining region residues and lipid antigen hydrophilic moieties in the recognition of a CD1-lipid complex. J Immunol 168(8):3933–3940PubMedCrossRefGoogle Scholar
  107. 107.
    Moody DB, Reinhold BB, Guy MR, Beckman EM, Frederique DE, Furlong ST, Ye S, Reinhold VN, Sieling PA, Modlin RL, Besra GS, Porcelli SA (1997) Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science 278(5336):283–286PubMedCrossRefGoogle Scholar
  108. 108.
    Van Rhijn I, Kasmar A, de Jong A, Gras S, Bhati M, Doorenspleet ME, de Vries N, Godfrey DI, Altman JD, de Jager W, Rossjohn J, Moody DB (2013) A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nat Immunol 14(7):706–713.  https://doi.org/10.1038/ni.2630 PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Van Rhijn I, Moody DB (2015) CD1 and mycobacterial lipids activate human T cells. Immunol Rev 264(1):138–153.  https://doi.org/10.1111/imr.12253 PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Layre E, Collmann A, Bastian M, Mariotti S, Czaplicki J, Prandi J, Mori L, Stenger S, De Libero G, Puzo G, Gilleron M (2009) Mycolic acids constitute a scaffold for mycobacterial lipid antigens stimulating CD1-restricted T cells. Chem Biol 16(1):82–92.  https://doi.org/10.1016/j.chembiol.2008.11.008 PubMedCrossRefGoogle Scholar
  111. 111.
    Kasmar AG, van Rhijn I, Cheng TY, Turner M, Seshadri C, Schiefner A, Kalathur RC, Annand JW, de Jong A, Shires J, Leon L, Brenner M, Wilson IA, Altman JD, Moody DB (2011) CD1b tetramers bind alphabeta T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans. J Exp Med 208(9):1741–1747.  https://doi.org/10.1084/jem.20110665 PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Gras S, Van Rhijn I, Shahine A, Cheng TY, Bhati M, Tan LL, Halim H, Tuttle KD, Gapin L, Le Nours J, Moody DB, Rossjohn J (2016) T cell receptor recognition of CD1b presenting a mycobacterial glycolipid. Nat Commun 7:13257.  https://doi.org/10.1038/ncomms13257 PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Batuwangala T, Shepherd D, Gadola SD, Gibson KJ, Zaccai NR, Fersht AR, Besra GS, Cerundolo V, Jones EY (2004) The crystal structure of human CD1b with a bound bacterial glycolipid. J Immunol 172(4):2382–2388PubMedCrossRefGoogle Scholar
  114. 114.
    Garcia-Alles LF, Collmann A, Versluis C, Lindner B, Guiard J, Maveyraud L, Huc E, Im JS, Sansano S, Brando T, Julien S, Prandi J, Gilleron M, Porcelli SA, de la Salle H, Heck AJ, Mori L, Puzo G, Mourey L, De Libero G (2011) Structural reorganization of the antigen-binding groove of human CD1b for presentation of mycobacterial sulfoglycolipids. Proc Natl Acad Sci USA 108(43):17755–17760.  https://doi.org/10.1073/pnas.1110118108 PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Gilleron M, Stenger S, Mazorra Z, Wittke F, Mariotti S, Bohmer G, Prandi J, Mori L, Puzo G, De Libero G (2004) Diacylated sulfoglycolipids are novel mycobacterial antigens stimulating CD1-restricted T cells during infection with Mycobacterium tuberculosis. J Exp Med 199(5):649–659.  https://doi.org/10.1084/jem.20031097 PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Moody DB, Young DC, Cheng TY, Rosat JP, Roura-Mir C, O’Connor PB, Zajonc DM, Walz A, Miller MJ, Levery SB, Wilson IA, Costello CE, Brenner MB (2004) T cell activation by lipopeptide antigens. Science 303(5657):527–531.  https://doi.org/10.1126/science.1089353 PubMedCrossRefGoogle Scholar
  117. 117.
    Zajonc DM, Crispin MD, Bowden TA, Young DC, Cheng TY, Hu J, Costello CE, Rudd PM, Dwek RA, Miller MJ, Brenner MB, Moody DB, Wilson IA (2005) Molecular mechanism of lipopeptide presentation by CD1a. Immunity 22(2):209–219.  https://doi.org/10.1016/j.immuni.2004.12.009 PubMedCrossRefGoogle Scholar
  118. 118.
    Snow GA, White AJ (1969) Chemical and biological properties of mycobactins isolated from various mycobacteria. Biochem J 115(5):1031–1050PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Layre E, Paepe DC, Larrouy-Maumus G, Vaubourgeix J, Mundayoor S, Lindner B, Puzo G, Gilleron M (2011) Deciphering sulfoglycolipids of Mycobacterium tuberculosis. J Lipid Res 52(6):1098–1110.  https://doi.org/10.1194/jlr.M013482 PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Scharf L, Li NS, Hawk AJ, Garzon D, Zhang T, Fox LM, Kazen AR, Shah S, Haddadian EJ, Gumperz JE, Saghatelian A, Faraldo-Gomez JD, Meredith SC, Piccirilli JA, Adams EJ (2010) The 2.5 A structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity 33(6):853–862.  https://doi.org/10.1016/j.immuni.2010.11.026 PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Roy S, Ly D, Li NS, Altman JD, Piccirilli JA, Moody DB, Adams EJ (2014) Molecular basis of mycobacterial lipid antigen presentation by CD1c and its recognition by alphabeta T cells. Proc Natl Acad Sci USA 111(43):E4648–E4657.  https://doi.org/10.1073/pnas.1408549111 PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Van Rhijn I, van Berlo T, Hilmenyuk T, Cheng TY, Wolf BJ, Tatituri RV, Uldrich AP, Napolitani G, Cerundolo V, Altman JD, Willemsen P, Huang S, Rossjohn J, Besra GS, Brenner MB, Godfrey DI, Moody DB (2016) Human autoreactive T cells recognize CD1b and phospholipids. Proc Natl Acad Sci USA 113(2):380–385.  https://doi.org/10.1073/pnas.1520947112 PubMedCrossRefGoogle Scholar
  123. 123.
    Gadola SD, Zaccai NR, Harlos K, Shepherd D, Castro-Palomino JC, Ritter G, Schmidt RR, Jones EY, Cerundolo V (2002) Structure of human CD1b with bound ligands at 2.3 A, a maze for alkyl chains. Nat Immunol 3(8):721–726.  https://doi.org/10.1038/ni821 PubMedCrossRefGoogle Scholar
  124. 124.
    Dundas J, Ouyang Z, Tseng J, Binkowski A, Turpaz Y, Liang J (2006) CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic acids research 34(Web Server issue):W116–W118.  https://doi.org/10.1093/nar/gkl282 PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Schrodinger, LLC (2015) The PyMOL Molecular Graphics System, Version 1.7.6.4Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Stephanie Gras
    • 1
    • 2
  • Ildiko Van Rhijn
    • 3
    • 4
  • Adam Shahine
    • 1
    • 2
  • Jérôme Le Nours
    • 1
    • 2
  1. 1.Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery InstituteMonash UniversityClaytonAustralia
  2. 2.Australian Research Council Centre of Excellence in Advanced Molecular ImagingMonash UniversityClaytonAustralia
  3. 3.Division of Rheumatology, Immunology and AllergyBrigham and Women’s Hospital/Harvard Medical SchoolBostonUSA
  4. 4.Department of Infectious Diseases and Immunology, Faculty of Veterinary MedicineUniversity UtrechtUtrechtThe Netherlands

Personalised recommendations