Springer Seminars in Immunopathology

, Volume 22, Issue 3, pp 191–217

Antigen recognition by human γδ T cells: pattern recognition by the adaptive immune system

  • Craig T. Morita
  • Roy A. Mariuzza
  • Michael B. Brenner
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References

  1. 1.
    Alaibac M, Harms G, Zwingenberger K, Morris J, Yu R, Chu AC (1993) γδ T lymphocytes in oriental cutaneous leishmaniasis: occurrence and Vδ gene expression. Br J Dermatol 128: 388PubMedCrossRefGoogle Scholar
  2. 2.
    Allison JP, McIntyre BW, Bloch D (1982) Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol 129: 2293PubMedGoogle Scholar
  3. 3.
    Arden B, Clark SP, Kabelitz D, Mak TW (1995) Human T-cell receptor variable gene segment families. Immunogenetics 42: 455PubMedGoogle Scholar
  4. 4.
    Bahram S, Bresnahan M, Geraghty DE, Spies T (1994) A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci USA 91: 6259PubMedCrossRefGoogle Scholar
  5. 5.
    Balbi B, Valle MT, Oddera S, Giunti D, Manca F, Rossi GA, Allegra L (1993) T-lymphocytes with γδ+ Vδ2+ antigen receptors are present in increased proportions in a fraction of patients with tuberculosis or with sarcoidosis. Am Rev Respir Dis 148: 1685PubMedGoogle Scholar
  6. 6.
    Band H, Hochstenbach F, McLean J, Hata S, Krangel MS, Brenner MB (1987) Immunochemical proof that a novel rearranging gene encodes the T cell receptor δ subunit. Science 238: 682PubMedCrossRefGoogle Scholar
  7. 7.
    Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285: 727PubMedCrossRefGoogle Scholar
  8. 8.
    Beckman EM, Melian A, Behar SM, Sieling PA, Chatterjee D, Furlong ST, Matsumoto R, Rosat JP, Modlin RL, Porcelli SA (1996) CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family. J Immunol 157: 2795PubMedGoogle Scholar
  9. 9.
    Behr C, Poupot R, Peyrat M-A, Poquet Y, Constant P, Dubois P, Bonneville M, Fournie J-J (1996) Plasmodium falciparum Stimuli for human γδ T cells are related to phosphorylated antigens of mycobacteria. Infect Immun 64: 2892PubMedGoogle Scholar
  10. 10.
    Belman C, Espinosa E, Poupot R, Peyrat M-A, Guiraud M, Poquet Y, Bonneville M, Fournié J-J (1999) 3-Formyl-l-butyl pyrophosphate a novel mycobacterial metabolite-activating human γδ T cells. J Biol Chem 274: 32079CrossRefGoogle Scholar
  11. 11.
    Bendelac A, Rivera MN, Park SH, Roark JH (1997) Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15: 535PubMedCrossRefGoogle Scholar
  12. 12.
    Bender A, Kabelitz D (1992) Preferential activation of peripheral blood Vγ9+ γ/δ T cells by group A, B and C but not group D or F Streptococci. Clin Exp Immunol 89: 301PubMedGoogle Scholar
  13. 13.
    Ben-Smith A, Goodall JC, Gaston JS, Winer JB (1997) Stimulation of peripheral blood lymphocytes with Campylobacter jejuni generates a γδ T cell response in patients with Guillain- Barré Syndrome. Clin Exp Immunol 109: 121PubMedCrossRefGoogle Scholar
  14. 14.
    Bertotto A, Gerli R, Spinozzi F, Muscat C, Scalise F, Castellucci G, Sposito M, Candio F, Vaccaro R (1993) Lymphocytes bearing the γδ T cell receptor in acute Brucella melitensis infection. Eur J Immunol 23: 1177PubMedCrossRefGoogle Scholar
  15. 15.
    Bigby M, Markowitz JS, Bleicher PA, Grusby MJ, Simha S, Siebrecht M, Wagner M, Nagler AC, Glimcher LH (1993) Most γδ T cells develop normally in the absence of MHC class II molecules. J Immunol 151: 4465PubMedGoogle Scholar
  16. 16.
    Bluestone JA, Cron RQ, Cotterman M, Houlden BA, Matis LA (1988) Structure and specificity of T cell receptor γ/δ on major histocompatibility complex antigen-speeifie CD3+, CD4, CD8 T lymphocytes. J Exp Med 168: 1899PubMedCrossRefGoogle Scholar
  17. 17.
    Boismenu R, Havran WL (1994) Modulation of epithelial cell growth by intraepithelial γδ T cells. Science 266: 1253PubMedCrossRefGoogle Scholar
  18. 18.
    Bonneville M, Ito K, Krecko EG, Itohara S, Kappes D, Ishida I, Kanagawa O, Janeway CA, Murphy DB, Tonegawa S (1989) Recognition of a self major histocompatibility complex TL region product by γδ T-cell reeeptors. Proc Natl Acad Sci USA 86: 5928PubMedCrossRefGoogle Scholar
  19. 19.
    Bork P, Holm L, Sander C (1994) The Immunoglobulin fold. Structural Classification, sequence patterns and common core. J Mol Biol 242: 309PubMedGoogle Scholar
  20. 20.
    Born W, Cady C, Jones-Carson J, Mukasa A, Lahn M, O’Brien R (1999) Immunoregulatory functions of γδ T cells. Adv Immunol 71: 77PubMedCrossRefGoogle Scholar
  21. 21.
    Born W, Hall L, Dallas A, Boymel J, Shinnick T, Young D, Brennan P, O’Brien R (1990) Recognition of a peptide antigen by heat shock-reactive γδ T lymphocytes. Science 249: 67PubMedCrossRefGoogle Scholar
  22. 22.
    Bosnes V, Qvigstad E, Lundin KE, Thorsby E (1990) Recognition of a particular HLA-DQ heterodimer by a human γ/δ T cell clone. Eur J Immunol 20: 1429PubMedCrossRefGoogle Scholar
  23. 23.
    Brando C, Shevach EM (1995) Engagement of the vitronectin receptor (αVβ3) on murine T cells stimulates tyrosine phosphorylation of a 115-kDa protein. J Immunol 154: 2005PubMedGoogle Scholar
  24. 24.
    Brenner M, Porcelli S (1997) Antigen presentation: a balanced diet. Science 277: 332PubMedCrossRefGoogle Scholar
  25. 25.
    Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, Seidman JG, Ip S, Rosen F, Krangel MS (1986) Identification of a putative second T-cell receptor. Nature 322: 145PubMedCrossRefGoogle Scholar
  26. 26.
    Bukowski JF, Morita CT, Band H, Brenner MB (1998) Crucial role of TCRγ chain junctional region in prenyl pyrophosphate antigen recognition by γδ T cells. J Immunol 161: 286PubMedGoogle Scholar
  27. 27.
    Bukowski JF, Morita CT, Brenner MB (1999) Human γδ T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity 11: 57PubMedCrossRefGoogle Scholar
  28. 28.
    Bukowski JF, Morita CT, Tanaka Y, Bloom BR, Brenner MB, Band H (1995) Vγ2Vδ2 TCR-dependent recognition of non-peptide antigens and Daudi cells analyzed by TCR gene transfer. J Immunol 154: 998PubMedGoogle Scholar
  29. 29.
    Burdin N, Brossay L, Kronenberg M (1999) Immunization with α-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis. Eur J Immunol 29: 2014PubMedCrossRefGoogle Scholar
  30. 30.
    Caldwell CW, Everett ED, McDonald G, Yesus YW, Roland WE (1995) Lymphocytosis of γ/δ T cells in human ehrlichiosis. Am J Clin Pathol 103: 761PubMedGoogle Scholar
  31. 31.
    Chien Y-h, Jores R, Crowley MP (1996) Recognition by γ/δ T cells. Annu Rev Immunol 14: 511PubMedCrossRefGoogle Scholar
  32. 32.
    Chien Y-h, Iwashima M, Kaplan KB, Elliott JF, Davis MM (1987) A new T-cell receptor gene located within the a locus and expressed early in T-cell differentiation. Nature 327: 677PubMedCrossRefGoogle Scholar
  33. 33.
    Chothia C, Lesk AM, Tramontano A, Levitt M, Smith-Gill SJ, Air G, Sheriff S, Padlan EA, Davies D, Tulip WR, Colman PM, Spinelli S, Alzari PM, Poljak RJ (1989) Conformations of Immunoglobulin hypervariable regions. Nature 342: 877PubMedCrossRefGoogle Scholar
  34. 34.
    Ciccone E, Viale O, Pende D, Mainati M, Battista FG, Barocci S, Moretta A, Moretta L (1989) Specificity of human T lymphocytes expressing a γ/δ T cell antigen receptor. Recognition of a polymorphie determinant of HLA class I molecules by a γ/δ clone. Eur J Immunol 19: 1267PubMedCrossRefGoogle Scholar
  35. 35.
    Constant P, Davodeau F, Peyrat M-A, Poquet Y, Puzo G, Bonneville M, Fournié J-J (1994) Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands. Science 264: 267PubMedCrossRefGoogle Scholar
  36. 36.
    Constant P, Poquet Y, Peyrat M-A, Davodeau F, Bonneville M, Fournié J-J (1995) The antituberculous Mycobacterium bovis BCG Vaccine is an attenuated mycobacterial producer of phosphorylated nonpeptidic antigens for human γδ T cells. Infect Immun 63: 4628PubMedGoogle Scholar
  37. 37.
    Correa I, Bix M, Liao NS, Zijlstra M, Jaenisch R, Raulet D (1992) Most γδ T cells develop normally in β2-microglobulin-deficient mice. Proc Natl Acad Sci USA 89: 653PubMedCrossRefGoogle Scholar
  38. 38.
    Crowley MP, Faher AM, Baumgarth N, Hampl J, Gutgemann I, Teyton L, Chien Y-H (2000) A population of murine γδ T cells recognized an inducible MHC class Ib molecule. Science 287: 314PubMedCrossRefGoogle Scholar
  39. 39.
    Crowley MP, Reich Z, Mavaddat N, Altman JD, Chien Y-H (1997) The recognition of the nonclassical major histocompatibility complex (MHC) class I molecule, T10, by the γδ T cell. G8. J Exp Med 185: 1223PubMedCrossRefGoogle Scholar
  40. 40.
    Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, Kaneko Y, Koseki H, Kanno M, Taniguchi M (1997) Requirement for Vαl4 NKT cells in IL-12-mediated rejection of tumors. Science 278: 1623PubMedCrossRefGoogle Scholar
  41. 41.
    Cui J, Watanabe N, Kawano T, Yamashita M, Kamata T, Shimizu C, Kimura M, Shimizu E, Koike J, Koseki H, Tanaka Y, Taniguchi M, Nakayama T (1999) Inhibition of T helper cell type 2 cell differentiation and Immunoglobulin E response by ligand-activated Vα14 natural killer T cells. J Exp Med 190: 783PubMedCrossRefGoogle Scholar
  42. 42.
    Davis MM, Bjorkman PJ (1988) T-cell antigen receptor genes and T-cell recognition. Nature 334: 395PubMedCrossRefGoogle Scholar
  43. 43.
    Davodeau F, Peyrat M-A, Hallet M-M, Gaschet J, Houde I, Vivien R, Vie H, Bonneville M (1993) Close correlation between Daudi and mycobacterial antigen recognition by human γδ T cells and expression of V9JPClγ/V2DJCδ-encoded T cell receptors. J Immunol 151: 1214PubMedGoogle Scholar
  44. 44.
    De Libero G, Casorati G, Giachino C, Carbonara C, Migone N, Matzinger P, Lanzavecchia A (1991) Selection by two powerful antigens may account for the presence of the major population of human peripheral γ/δ T cells. J Exp Med 173: 1311PubMedCrossRefGoogle Scholar
  45. 45.
    Del Porto P, D’Amato M, Fiorillo MT, Tuosto L, Piccolella E, Sorrentino R (1994) Identification of a novel HLA-B27 subtype by restriction analysis of a cytotoxic γδ T cell clone. J Immunol 153: 3093PubMedGoogle Scholar
  46. 46.
    Delfau M-H, Hance AJ, Lecossier D, Vilmer E, Grandchamp B (1992) Restricted diversity of Vγ9-JP rearrangements in unstimulated human γ/δ T lymphocytes. Eur J Immunol 22: 2437PubMedCrossRefGoogle Scholar
  47. 47.
    Dent AL, Matis LA, Hooshmand F, Widacki SM, Bluestone JA, Hedrick SM (1990) Self-reactive γδ T cells are eliminated in the thymus. Nature 343: 714PubMedCrossRefGoogle Scholar
  48. 48.
    Dieli F, Sireci G, Di Sano C, Champagne E, Fourniè JJ, Salerno JI (1999) Predominance of Vγ9/Vδ2 T lymphocytes in the cerebrospinal fluid of children with tuberculous meningitis: reversal after chemotherapy. Mol Med 5: 301PubMedGoogle Scholar
  49. 49.
    Ding YH, Smith KJ, Garboczi DN, Utz U, Biddison WE, Wiley DC (1998) Two human T cell receptors bind in a similar diagonal mode to the HLA- A2/Tax peptide complex using different TCR amino acids. Immunity 8: 403PubMedCrossRefGoogle Scholar
  50. 50.
    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: 331PubMedCrossRefGoogle Scholar
  51. 51.
    Exley M, Garcia J, Balk SP, Porcelli S (1997) Requirements for CD1d recognition by human invariant Vα24+ CD4CD8 T cells. J Exp Med 186: 109PubMedCrossRefGoogle Scholar
  52. 52.
    Falini B, Flenghi L, Pileri S, Pelicci P, Fagioli M, Martelli MF, Moretta L, Ciccone E (1989) Distribution of T cells bearing different forms of the T cell receptor γ/δ in normal and pathological human tissues. J Immunol 143: 2480PubMedGoogle Scholar
  53. 53.
    Fan ZC, Shan L, Guddat LW, He XM, Gray WR, Raison RL, Edmundson AB (1992) Three-dimensional structure of an Fv from a human IgM Immunoglobulin. J Mol Biol 228: 188PubMedCrossRefGoogle Scholar
  54. 54.
    Faure F, Jitsukawa S, Miossec C, Hercend T (1990) CD1c as a target recognition structure for human T lymphocytes: analysis with peripheral blood γ/δ cells. Eur J Immunol 20: 703PubMedCrossRefGoogle Scholar
  55. 55.
    Fearon DT, Locksley RM (1996) The instructive role of innate immunity in the acquired immune response. Science 272: 50PubMedCrossRefGoogle Scholar
  56. 56.
    Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H (1995) Differential production of interferon-γ and interleukin-4 in response to Thl- and Th2-stimulating pathogens by γδ T cells in vivo. Nature 373: 255PubMedCrossRefGoogle Scholar
  57. 57.
    Fisch P, Malkovsky M, Kovats S, Sturm E, Braakman E, Klein BS, Voss SD, Morrissey LW, DeMars R, Welch WJ, Bolhuis RLH, Sondel PM (1990) Recognition by human Vγ9/Vδ2 T cells of a GroEL homolog on Daudi Burkitt’s lymphoma cells. Science 250: 1269PubMedCrossRefGoogle Scholar
  58. 58.
    Fisch P, Meuer E, Pende D, Rothenfusser S, Viale O, Kock S, Ferrone S, Fradelizi D, Klein G, Moretta L, Rammensee H-G, Boon T, Coulie P, Bruggen P van der (1997) Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vγ9Vδ2 T cells in tumor immunity. Eur J Immunol 27: 3368PubMedCrossRefGoogle Scholar
  59. 59.
    Fischer S, Scheffler A, Kabelitz D (1996) Activation of human γδ T-cells by heat-treated mistletoe plant extracts. Immunol Lett 52: 69PubMedCrossRefGoogle Scholar
  60. 60.
    Fischer S, Scheffler A, Kabelitz D (1997) Stimulation of the specific immune system by mistletoe extracts. Anticancer Drugs 8: S33Google Scholar
  61. 61.
    Fisher AG, Ceredig R (1992) Human peripheral blood γδ T cells respond to antigens of Plasmodium falciparum. Int Immunol 4: 33CrossRefGoogle Scholar
  62. 62.
    Flament C, Benmerah A, Bonneville M, Triebel F, Mami-Chouaib F (1994) Human TCR-γ/δ alloreactive response to HLA-DR molecules. Comparison with response of TCR-α/β. J Immunol 153: 2890PubMedGoogle Scholar
  63. 63.
    Garboczi DN, Ghosh P, Utz U, Fan QR, Biddison WE, Wiley DC (1996) Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384: 134PubMedCrossRefGoogle Scholar
  64. 64.
    Garcia KC, Teyton L, Wilson IA (1999) Structural basis of T cell recognition. Annu Rev Immunol 17: 369PubMedCrossRefGoogle Scholar
  65. 65.
    Goerlich R, Hacker G, Pfeffer K, Heeg K, Wagner H (1991) Plasmodium falciparum merozoites primarily stimulate the Vγ9 subset of human γ/δ T cells. Eur J Immunol 21: 2613PubMedCrossRefGoogle Scholar
  66. 66.
    Goodier M, Fey P, Eichmann K, Langhorne J (1992) Preferential expansion of Vγ9Vδ2 T cells following Stimulation of peripheral blood lymphocytes with extracts of Plasmodium falciparum. Int Immunol 4: 361CrossRefGoogle Scholar
  67. 67.
    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: 195PubMedCrossRefGoogle Scholar
  68. 68.
    Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T (1996) Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 93: 12445PubMedCrossRefGoogle Scholar
  69. 69.
    Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T (1999) Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB. Proc Natl Acad Sci USA 96: 6879PubMedCrossRefGoogle Scholar
  70. 70.
    Groh V, Steinle A, Bauer S, Spies T (1998) Recognition of stress-induced MHC molecules by intestinal epithelial γδ T cells. Science 279: 1737PubMedCrossRefGoogle Scholar
  71. 71.
    Guo Y, Ziegler HK, Safley SA, Niesei DW, Vaidya S, Klimpel GR (1995) Human T-cell recognition of Listeria monocytogenes: recognition of listeriolysin O by TcRαβ+ and TcRyγδ+ T cells. Infect Immun 63: 2288PubMedGoogle Scholar
  72. 72.
    Hacker G, Kromer S, Heeg K, Ivanyi J, Wagner H, Pfeffer K (1992) Opportunist mycobacteria express ligands that stimulate produetion of human Vγ9Vδ2 T lymphocytes. Infect Immun 60: 2753PubMedGoogle Scholar
  73. 73.
    Halary F, Peyrat M-A, Champagne E, Lopez-Botet M, Moretta A, Moretta L, Vié H, Fournié J-J, Bonneville M (1997) Control of self-reactive cytotoxic T lymphocytes expressing γδ T cell receptors by natural killer inhibitory receptors. Eur J Immunol 27: 2812PubMedCrossRefGoogle Scholar
  74. 74.
    Hara T, Mizuno Y, Takaki K, Takada H, Akeda H, Aoki T, Nagata M, Ueda K, Matsuzaki G, Yoshikai Y, Nomoto K (1992) Predominant activation and expansion of Vγ9-bearing γδ T cells in vivo as well as in vitro in Salmonella infection. J Clin Invest 90: 204PubMedCrossRefGoogle Scholar
  75. 75.
    Haregewoin A, Singh B, Gupta RS, Finberg RW (1991) A mycobacterial heat-shock protein-responsive γδ T cell clone also responds to the homologous human heat-shock protein: a possible link between infection and autoimmunity. J Infect Dis 163: 156PubMedGoogle Scholar
  76. 76.
    Haregewoin A, Soman G, Hom RC, Finberg RW (1989) Human γδ+ T cells respond to mycobacterial heat-shock protein. Nature 340: 309PubMedCrossRefGoogle Scholar
  77. 77.
    Haskins K, Kubo R, White J, Pigeon M, Kappler J, Marrack P (1983) The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med 157: 1149PubMedCrossRefGoogle Scholar
  78. 78.
    Hata S, Brenner M, Krangel M (1987) Identification of putative human T cell receptor δ complementary DNA clones. Science 238: 678PubMedCrossRefGoogle Scholar
  79. 79.
    Havran WL, Chien Y-H, Allison JP (1991) Recogntion of self antigens by skin-derived T cells with invariant γδ receptors. Science 252: 1430PubMedCrossRefGoogle Scholar
  80. 80.
    Hermann E, Lohse AW, Mayet WJ, Van der Zee R, Van Eden W, Probst P, Poralla T, Meyer zum Buschenfelde K-H, Fleischer B (1992) Stimulation of synovial fluid mononuclear cells with the human 65-kD heat shock protein or with live enterobacteria leads to preferential expansion of TCR-γδ+ lymphocytes. Clin Exp Immunol 89: 427PubMedGoogle Scholar
  81. 81.
    Ho M, Webster HK, Tongtawe P, Pattanapanyasat K, Weidanz WP (1990) Increased γδ T cells in acute Plasmodium falciparum malaria. Immunol Lett 25: 139PubMedCrossRefGoogle Scholar
  82. 82.
    Holoshitz J, Koning F, Coligan JE, De Bruyn J, Strober S (1989) Isolation of CD4 CD8 mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature 339: 226PubMedCrossRefGoogle Scholar
  83. 83.
    Holoshitz J, Vila LM, Keroack BJ, McKinley DR, Bayne NK (1992) Dual antigenic recognition by cloned human γδ T cells. J Clin Invest 89: 308PubMedCrossRefGoogle Scholar
  84. 84.
    Ito M, Kojiro N, Ikeda T, Ito T, Funada J, Kokubu T (1992) Increased proportions of peripheral blood γδ T cells in patients with pulmonary tuberculosis. Chest 102: 195PubMedCrossRefGoogle Scholar
  85. 85.
    Janeway CA Jr (1998) The road less traveled by: the role of innate immunity in the adaptive immune response. J Immunol 161: 539PubMedGoogle Scholar
  86. 86.
    Jarry A, Cerf-Bensussan N, Brousse N, Selz F, Guy-Grand D (1990) Subsets of CD3+ (T cell receptor α/β or γ/δ) and CD3 lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol 20: 1097PubMedCrossRefGoogle Scholar
  87. 87.
    Johnson RM, Lancki DW, Sperling AI, Dick RF, Spear PG, Fitch FW, Bluestone JA (1992) A murine CD4, CD8 T cell receptor-γδ T lymphocyte clone specific for herpes simplex virus glycoprotein I. J Immunol 148: 983PubMedGoogle Scholar
  88. 88.
    Jomaa H, Feurle J, Luhs K, Kunzmann V, Tony HP, Herderich M, Wilhelm M (1999) Vγ9/Vδ2 T cell activation induced by bacterial low molecular mass Compounds depends on the 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis. FEMS Immunol Med Microbiol 25: 371PubMedGoogle Scholar
  89. 89.
    Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Turbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E (1999) Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285: 1573PubMedCrossRefGoogle Scholar
  90. 90.
    Jouen-Beades F, Paris E, Dieulois C, Lemeland J-F, Barre-Dezelus V, Marret S, Humbert G, Leroy J, Tron F (1997) In vivo and in vitro activation and expansion of γδ T cells during Listeria monocytogenes infection in humans. Infect Immun 65: 4267PubMedGoogle Scholar
  91. 91.
    Joyce S, Woods AS, Yewdell JW, Bennink JR, De Silva AD, Boesteanu A, Balk SP, Cotter RJ, Brutkiewicz RR (1998) Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 279: 1541PubMedCrossRefGoogle Scholar
  92. 92.
    Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller C (1991) Sequences of Proteins of Immunological Interest, 5th ed. Public Health Services, National Institutes of Health, Washington, D.C.Google Scholar
  93. 93.
    Kabelitz D, Bender A, Schondelmaier S, da Silva Lobo ML, Janssen O (1990) Human cytotoxic lymphocytes. V. Frequency and specificity of γδ+ cytotoxic lymphocyte precursors activated by allogeneic or autologous stimulator cells. J Immunol 145: 2827PubMedGoogle Scholar
  94. 94.
    Kabelitz D, Bender A, Schondelmaier S, Schoel B, Kaufmann SHE (1990) A large fraction of human peripheral blood γ/δ+ T cells is activated by Mycobacterium tuberculosis but not by its 65-kD heat shock protein. J Exp Med 171: 667PubMedCrossRefGoogle Scholar
  95. 95.
    Kaliyaperumal A, Falchetto R, Cox A, Dick R, II Shabanowitz J, Chien Y-H, Matis L, Hunt DF, Bluestone JA (1995) Functional expression and recognition of nonclassical MHC class I T10b is not peptide-dependent. J Immunol 155: 2379PubMedGoogle Scholar
  96. 96.
    Kaur I, Voss SD, Gupta RS, Schell K, Fisch P, Sondel PM (1993) Human peripheral γδ T cells recognize hsp60 molecules on Daudi Burkitt’s lymphoma cells. J Immunol 150: 2046PubMedGoogle Scholar
  97. 97.
    Kersten CM, McCluskey RT, Boyle LA, Kurnick JT (1996) Escherichia coli and Pseudomonas aeruginosa induce expansion of Vδ2 cells in adult peripheral blood, but of Vδl cells in cord blood. J Immunol 157: 1613PubMedGoogle Scholar
  98. 98.
    Kikuchi GE, Roberts K, Shevach E, Coligan JE (1992) Gene transfer demonstrates that the V-γ1.1 C-γ 4 V-δ6 C-δ T cell receptor is essential for autoreactivity. J Immunol 148: 1302PubMedGoogle Scholar
  99. 99.
    Kim HT, Nelson EL, Clayberger C, Sanjanwala M, Sklar J, Krensky AM (1995) γδ T cell recognition of tumor Ig peptide. J Immunol 154: 1614PubMedGoogle Scholar
  100. 100.
    Köhler S, Delwiche CF, Denny PW, Tilney LG, Webster P, Wilson RJ, Palmer JD, Roos DS (1997) A plastid of probable green algal origin in apicomplexan parasites. Science 275: 1485PubMedCrossRefGoogle Scholar
  101. 101.
    Koide J, Rivas A, Engleman EG (1989) Natural killer (NK)-like cytotoxic activity of allospecific T cell receptor-γδ+ T cell clones. Distinct receptor-ligand interactions mediate NK-like and allospecific cytotoxicity. J Immunol 142: 4161PubMedGoogle Scholar
  102. 102.
    Kozbor D, Trinchieri G, Monos DS, Isobe M, Russo G, Haney JA, Zmijewski C, Croce CM (1989) Human TCR-γ+/ δ+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion. J Exp Med 169: 1847PubMedCrossRefGoogle Scholar
  103. 103.
    Krangel MS, Yssel H, Brocklehurst C, Spits H (1990) A distinct wave of human T cell receptor γ/δ lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production. J Exp Med 172: 847PubMedCrossRefGoogle Scholar
  104. 104.
    Lang F, Peyrat MA, Constant P, Davodeau F, David-Ameline J, Poquet Y, Vié H, Fournié JJ, Bonneville M (1995) Early activation of human Vγ9Vδ2 T cell broad cytotoxicity and TNF production by nonpeptidic mycobacterial ligands. J Immunol 154: 5986PubMedGoogle Scholar
  105. 105.
    Li H, Lebedeva MI, Llera AS, Fields BA, Brenner MB, Mariuzza RA (1998) Structure of the Vδ domain of a human γδ T-cell antigen receptor. Nature 391: 502PubMedCrossRefGoogle Scholar
  106. 106.
    Li P, Willie ST, Bauer S, Morris DL, Spies T, Strong RK (1999) Crystal structure of the MHC class I homolog MIC-A, a γδ T cell ligand. Immunity 10: 577PubMedCrossRefGoogle Scholar
  107. 107.
    Loh EY, Wang M, Bartkowiak J, Wiaderkiewicz R, Hyjek E, Wang Z, Kozbor D (1994) Gene transfer studies of T cell receptor-γδ recognition. Specificity for staphylococcal enterotoxin A is conveyed by Vγ9 alone. J Immunol 152: 3324PubMedGoogle Scholar
  108. 108.
    Matis LA, Fry AM, Cron RQ, Cotterman MM, Dick RF, Bluestone JA (1989) Structure and specificity of a class II MHC alloreactive γδ T cell receptor heterodimer. Science 245: 746PubMedCrossRefGoogle Scholar
  109. 109.
    McVay LD, Jaswal SS, Kennedy C, Hayday A, Carding SR (1998) The generation of human γδ T cell repertoires during fetal development. J Immunol 160: 5851PubMedGoogle Scholar
  110. 110.
    Meuer SC, Acuto O, Hussey RE, Hodgdon JC, Fitzgerald KA, Schlossman SF, Reinherz EL (1983) Evidence for the T3-associated 90 K heterodimer as the T-cell antigen receptor. Nature 303: 808PubMedCrossRefGoogle Scholar
  111. 111.
    Modlin RL, Pirmez C, Hofman FM, Torigian V, Uyemura K, Rea TH, Bloom BR, Brenner MB (1989) Lymphocytes bearing antigen-specific γδ T-cell receptors accumulate in human infectious disease lesions. Nature 339: 544PubMedCrossRefGoogle Scholar
  112. 112.
    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: 283PubMedCrossRefGoogle Scholar
  113. 113.
    Moody DB, Ulrichs T, Mühlecker W, Young DC, Gurcha SS, Grant E, Rosat J-P, Brenner MB, Costello CE, Besra GS, Porcelli SA(2000) CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium Tuberculosis infection. Nature 404: 884PubMedCrossRefGoogle Scholar
  114. 114.
    Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H, Bloom BR, Golan DE, Brenner MB (1995) Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells. Immunity 3: 495PubMedCrossRefGoogle Scholar
  115. 115.
    Morita CT, Lee HK, Leslie DS, Tanaka YT, Bukowski JF, Märker-Hermann E (1999) Recognition of nonpeptide prenyl pyrophosphate antigens by human γδ T cells. Microbes Infect 1: 175CrossRefGoogle Scholar
  116. 116.
    Morita CT, Parker CM, Brenner MB, Band H (1994) T cell receptor usage and functional capabilities of human γδ T cells at birth. J Immunol 153: 3979PubMedGoogle Scholar
  117. 117.
    Munk ME, Elser C, Kaufmann SHE (1996) Human γ/δ T-cell response to Listeria monocytogenes protein components in vitro. Immunology 87: 230PubMedCrossRefGoogle Scholar
  118. 118.
    Munk ME, Gatrill AJ, Kaufmann SHE (1990) Target cell lysis and IL-2 secretion by γ/δ T lymphocytes after activation with bacteria. J Immunol 145: 2434PubMedGoogle Scholar
  119. 119.
    Panchamoorthy G, McLean J, Modlin RL, Morita CT, Ishikawa S, Brenner MB, Band H (1991) A predominance of the T cell receptor Vγ2/Vδ2 subset in human mycobacteria-responsive T cells suggests germline gene encoded recognition. J Immunol 147: 3360PubMedGoogle Scholar
  120. 120.
    Parker CM, Groh V, Band H, Porcelli SA, Morita C, Fabbi M, Glass D, Strominger JL, Brenner MB (1990) Evidence for extrathymic changes in the T cell receptor γ/δ repertoire. J Exp Med 171: 1597PubMedCrossRefGoogle Scholar
  121. 121.
    Perera MK, Carter R, Goonewardene R, Mendis KN (1994) Transient increase in circulating γ/δ T cells during Plasmodium vivax malarial paroxysms. J Exp Med 179: 311PubMedCrossRefGoogle Scholar
  122. 122.
    Poquet Y, Constant P, Halary F, Peyrat M-A, Gilleron M, Davodeau F, Bonneville M, Fournié J-J (1996) A novel nucleotide-containing antigen for human blood γδ T lymphocytes. Eur J Immunol 26: 2344PubMedCrossRefGoogle Scholar
  123. 123.
    Poquet Y, Kroca M, Halary F, Stenmark S, Peyrat M-A, Bonneville M, Fournié JJ, Sjöstedt A (1998) Expansion of Vγ9Vδ2 T cells is triggered by Francisella tularensis-derived phosphoantigens in tularemia but not after tularemia vaccination. Infect Immun 66: 2107PubMedGoogle Scholar
  124. 124.
    Porcelli S, Brenner MB, Band H (1991) Biology of the human γδ T-cell receptor. Immunol Rev 120: 137PubMedCrossRefGoogle Scholar
  125. 125.
    Porcelli S, Brenner MB, Greenstein JL, Balk SP, Terhorst C, Bleicher PA (1989) Recognition of cluster of differentiation 1 antigens by human CD4CD8 cytolytic T lymphocytes. Nature 341: 447PubMedCrossRefGoogle Scholar
  126. 126.
    Porcelli S, Morita CT, Brenner MB (1992) CD1b restricts the response of human CD48 T lymphocytes to a microbial antigen. Nature 360: 593PubMedCrossRefGoogle Scholar
  127. 127.
    Porcelli S, Yockey CE, Brenner MB, Balk SP (1993) Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD48 α/β T cells demonstrates preferential use of several Vβ genes and an invariant TCR α chain. J Exp Med 178: 1PubMedCrossRefGoogle Scholar
  128. 128.
    Porcelli SA (1995) The CD1 family: a third lineage of antigen-presenting molecules. Adv Immunol 59: 1PubMedCrossRefGoogle Scholar
  129. 129.
    Porcelli SA, Brenner MB (1997) Antigen presentation: mixing oil and water. Current Biology 7: R508Google Scholar
  130. 130.
    Porcelli SA, Modlin RL (1999) The CD1 System: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annu Rev Immunol 17: 297PubMedCrossRefGoogle Scholar
  131. 131.
    Ranganathan G, Mukkada AJ (1995) Ubiquinone biosynthesis in Leishmania major promastigotes. Int J Parasitol 25: 279PubMedCrossRefGoogle Scholar
  132. 132.
    Rast JP, Anderson MK, Strang SJ, Luer C, Litman RT, Litman GW (1997) α, β, γ, and δ T cell antigen receptor genes arose early in vertebrate phylogeny. Immunity 6: 1PubMedCrossRefGoogle Scholar
  133. 133.
    Raziuddin S, Mir NA, El-Awad ME-H, Telmesani AW, Al-Janadi M (1994) γδ T lymphocytes and proinflammatory cytokines in bacterial meningitis. J Allergy Clin Immunol 93: 793PubMedCrossRefGoogle Scholar
  134. 134.
    Raziuddin S, Telmasani AW, El-Awad ME, Al-Amari O, Al-Janadi M (1992) γδ T cells and the immune response in visceral leishmaniasis. Eur J Immunol 22: 1143PubMedCrossRefGoogle Scholar
  135. 135.
    Rivas A, Koide J, Cleary ML, Engleman EG (1989) Evidence for involvement of the γ,δ T cell antigen receptor in cytotoxicity mediated by human alloantigen-specific T cell clones. J Immunol 142: 1840PubMedGoogle Scholar
  136. 136.
    Roberts K, Yokoyama WM, Kehn PJ, Shevach EM (1991) The vitronectin receptor serves as an accessory molecule for the activation of a subset of γδ T cells. J Exp Med 173: 231PubMedCrossRefGoogle Scholar
  137. 137.
    Rock EP, Sibbald PR, Davis MM, Chien Y-H (1994) CDR3 length in antigen-specific immune receptors. J Exp Med 179: 323PubMedCrossRefGoogle Scholar
  138. 138.
    Rohdich F, Wungsintaweekul J, Fellermeier M, Sagner S, Herz S, Kis K, Eisenreich W, Bacher A, Zenk MH (1999) Cytidine 5′-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol. Proc Natl Acad Sci USA 96: 11758PubMedCrossRefGoogle Scholar
  139. 139.
    Rohmer M (1999) The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants. Nat Prod Rep 16: 565PubMedCrossRefGoogle Scholar
  140. 140.
    Roussilhon C, Agrapart M, Ballet J-J, Bensussan A (1990) T lymphocytes bearing the γδ T cell receptor in patients with acute Plasmodium falciparum malaria. J Infect Dis 162: 283PubMedGoogle Scholar
  141. 141.
    Russo DM, Armitage RJ, Barral NM, Barral A, Grabstein KH, Reed SG (1993) Antigen-reactive γδ T cells in human leishmaniasis. J Immunol 151: 3712PubMedGoogle Scholar
  142. 142.
    Rust C, Orsini D, Kooy Y, Koning F (1993) Reactivity of human γδ T cells to staphylococcal enterotoxins: a restricted reaction pattern mediated by two distinct recognition pathways. Scand J Immunol 38: 89PubMedCrossRefGoogle Scholar
  143. 143.
    Rust CJJ, Verreck F, Victor H, Koning F (1990) Specific recognition of staphylococcal enterotoxin A by human T cells bearing receptors with the Vγ9 region. Nature 346: 572PubMedCrossRefGoogle Scholar
  144. 144.
    Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S (1984) Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature 309: 757PubMedCrossRefGoogle Scholar
  145. 145.
    Satyanarayana K, Hata S, Devlin P, Roncarolo MG, De Vries JE, Spits H, Strominger JL, Krangel MS (1988) Genomic Organization of the human T-cell antigen-receptor α/δ locus. Proc Natl Acad Sci USA 85: 8166PubMedCrossRefGoogle Scholar
  146. 146.
    Scalise F, Gerli R, Castellucci G, Spinozzi F, Fabietti GM, Crupi S, Sensi L, Britta R, Vaccaro R, Bertotto A (1992) Lymphocytes bearing the γδ T-cell receptor in acute toxoplasmosis. Immunology 76: 668PubMedGoogle Scholar
  147. 147.
    Schild H, Mavaddat N, Litzenberger C, Ehrich EW, Davis MM, Bluestone JA, Matis L, Draper RK, Chien Y-h (1994) The nature of major histocompatibility complex recognition by γδ T cells. Cell 76: 29PubMedCrossRefGoogle Scholar
  148. 148.
    Schneider T, Jahn HU, Liesenfeld O, Steinhoff D, Riecken EO, Zeitz M, Ullrich R (1997) The number and proportion of Vγ9/Vδ2 T cells rise significantly in the peripheral blood of patients after the onset of acute Coxiella burnetii infection. Clin Infect Dis 24: 261PubMedGoogle Scholar
  149. 149.
    Schwartz E, Shapiro R, Shina S, Bank I (1996) Delayed expansion of Vδ2+ and Vδl+ γδ T cells after acute Plasmodium falciparum and Plasmodium vivax malaria. J Allergy Clin Immunol 97: 1387PubMedCrossRefGoogle Scholar
  150. 150.
    Sciammas R, Johnson RM, Sperling AI, Brady W, Linsley PS, Spear PG, Fitch FW, Bluestone JA (1994) Unique antigen recognition by a herpesvirus-specific TCR-γδ cell. J Immunol 152: 5392PubMedGoogle Scholar
  151. 151.
    Sciammas R, Kodukula P, Tang Q, Hendricks RL, Bluestone JA (1997) T cell receptor-γ/δ cells protect mice from herpes simplex virus type 1-induced lethal encephalitis. J Exp Med 185: 1969PubMedCrossRefGoogle Scholar
  152. 152.
    Selin LK, Stewart S, Shen C, Mao HQ, Wilkins JA (1992) Reactivity of γδ T cells induced by the tumour cell line RPMI 8226: functional heterogeneity of clonal populations and role of GroEL heat shock proteins. Scand J Immunol 36: 107PubMedCrossRefGoogle Scholar
  153. 153.
    Singh N, Hong S, Scherer DC, Serizawa I, Burdin N, Kronenberg M, Koezuka Y, Van Kaer L (1999) Activation of NK T cells by CD1d and α-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J Immunol 163: 2373PubMedGoogle Scholar
  154. 154.
    Söderström K, Bucht A, Halapi E, Lundqvist C, Grönberg A, Nilsson E, Orsini DLM, Wal Y van de, Koning F, Hammarström M-L, Kiessling R (1994) High expression of Vγ8 is a shared feature of human γδ T cells in the epithelium of the gut and in the inflamed synovial tissue. J Immunol 152: 6017PubMedGoogle Scholar
  155. 155.
    Sottini A, Imberti L, Fiordalisi G, Primi D (1991) Plasmodium falciparum merozoites primarily stimulate the Vγ9 subset of human γ/δ T cells. Eur J Immunol 21: 2613CrossRefGoogle Scholar
  156. 156.
    Spada FM, Grant EP, Peters PJ, Sugita M, Melián A, Leslie DS, Lee HK, Donselaar E van, Hanson DA, Krensky AM, Majdic O, Porcelli SA, Morita CT, Brenner MB (2000) Self recognition of CD1 by γδ T cells: implications for innate immunity. J Exp Med 191: 937PubMedCrossRefGoogle Scholar
  157. 157.
    Spits H, Paliard X, Engelhard VH, Vries JE de (1990) Cytotoxic activity and lymphokine production of T cell receptor (TCR)-αβ+ and TCR-γδ+ cytotoxic T lymphocyte (CTL) clones recognizing HLA-A2 and HLA-A2 mutants. Recognition of TCR-γδ+ CTL clones is affected by mutations at positions 152 and 156. J Immunol 144: 4156PubMedGoogle Scholar
  158. 158.
    Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melian A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL (1998) An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282: 121PubMedCrossRefGoogle Scholar
  159. 159.
    Sturmhofel K, Brando C, Martinon F, Shevach EM, Coligan JE (1995) Antigen-independent, integrin-mediated T cell activation. J Immunol 154: 2104PubMedGoogle Scholar
  160. 160.
    Subauste CS, Chung JY, Do D, Koniaris AH, Hunter CA, Montoya JG, Porcelli S, Remington JS (1995) Preferential activation and expansion of human peripheral blood γδ T cells in response to Toxoplasma gondii in vitro and their cytokine produetion and cytotoxic activity against T. gondii-infected cells. J Clin Invest 96: 610PubMedCrossRefGoogle Scholar
  161. 161.
    Sumida T, Maeda T, Takahashi H, Yoshida S, Yonaha F, Sakamoto A, Tomioka H, Koike T, Yoshida S (1992) Predominant expansion of Vγ9/Vδ2 T cells in a tularemia patient. Infect Immun 60: 2554PubMedGoogle Scholar
  162. 162.
    Szalay G, Ladel CH, Blum C, Brossay L, Kronenberg M, Kaufmann SHE (1999) Anti-CD1 monoclonal antibody treatment reverses the production patterns of TGF-β2 and Th1 cytokines and ameliorates listeriosis in mice. J Immunol 162: 6955PubMedGoogle Scholar
  163. 163.
    Tanaka Y, Morita CT, Tanaka Y, Nieves E, Brenner MB, Bloom BR (1995) Natural and synthetic non-peptide antigens recognized by human γδ T cells. Nature 375: 155PubMedCrossRefGoogle Scholar
  164. 164.
    Tanaka Y, Sano S, Nieves E, De Libero G, Roca D, Modlin RL, Brenner MB, Bloom BR, Morita CT (1994) Nonpeptide ligands for human γδ T cells. Proc Natl Acad Sci USA 91: 8175PubMedCrossRefGoogle Scholar
  165. 165.
    Ueta C, Tsuyuguchi I, Kawasumi H, Takashima T, Toba H, Kishimoto S (1994) Increase of γ/δ T cells in hospital workers who are in close contact with tuberculosis patients. Infect Immun 62: 5434PubMedGoogle Scholar
  166. 166.
    Weintraub BC, Jackson MR, Hedrick SM (1994) γδ T cells can recognize nonclassical MHC in the absence of conventional antigenic peptides. J Immunol 153: 3051PubMedGoogle Scholar
  167. 167.
    Wilhelm M, Tony H-P (1994) An in vitro model for the expansion of Vγ9δ2 T lymphocytes during development. Scand J Immunol 40: 521PubMedCrossRefGoogle Scholar
  168. 168.
    Wright A, Lee JE, Link MP, Smith SD, Carroll W, Levy R, Clayberger C, Krensky AM (1989) Cytotoxic T lymphocytes specific for self tumor Immunoglobulin express T cell receptor δ chain. J Exp Med 169: 1557PubMedCrossRefGoogle Scholar
  169. 169.
    Young JL, Goodall JC, Beacock-Sharp H, Gaston JS (1997) Human γδ T-cell recognition of Yersinia enterocolitica. Immunology 91: 503PubMedCrossRefGoogle Scholar
  170. 170.
    Zeng Z-H, Castaño 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: 339PubMedCrossRefGoogle Scholar
  171. 171.
    Zhang Y, Cado D, Asarnow DM, Komori T, Alt FW, Raulet DH, Allison JP (1995) The role of short homology repeats and TdT in generation of the invariant γδ antigen receptor repertoire in the fetal thymus. Immunity 3: 439PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Craig T. Morita
    • 1
  • Roy A. Mariuzza
    • 2
  • Michael B. Brenner
    • 3
  1. 1.Division of Rheumatology, Department of Internal Medicine, and the Interdisciplinary Group in Immunology, EMRB 340FUniversity of IowaIowa CityUSA
  2. 2.Center for Advanced Research in BiotechnologyUniversity of Maryland Biotechnology InstituteRockvilleUSA
  3. 3.Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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