The Role of Heat Shock Proteins in the Elicitation of Immune Responses

  • Charles A Gullo
  • Paul Macary
  • Michael Graner
Part of the Heat Shock Proteins book series (HESP, volume 1)


Heat Shock Proteins (HSP), well known for their protein/polpypetide chaperone activities, display a remarkable ability to elicit peptide-based immune responses. The exact manner in which they do so, their physiological role in this process, and their distinct ability to promote adaptive immune response is the subject of this chapter. The first part of the chapter will deal with the general known antigenic stimulation properties of heat shock proteins, the second will deal with the separation of innate and adaptive immune responses as learned from studies with GP96, Hsp70, and Mycobacterium Hsp70 and finally the third will deal with the subject of chaperone rich cell lysates and means of isolating these HSP immunogenic complexes


Adjuvanticity antigen simulation HSP MHC 


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  1. Anthony, L. S., Wu, H., Sweet, H., Turnnir, C., Boux, L. J. and Mizzen, L. A. (1999) Priming of CD8+ CTL effector cells in mice by immunization with a stress protein-influenza virus nucleoprotein fusion molecule. Vaccine 17, 373–83.PubMedCrossRefGoogle Scholar
  2. Arnold, D., Faath, S., Rammensee, H. and Schild, H. (1995) Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96. J Exp Med 182, 885–9.PubMedCrossRefGoogle Scholar
  3. Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W., Koo, G. C. and Calderwood, S. K. (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6, 435–42.PubMedCrossRefGoogle Scholar
  4. Barbouche, R., Miquelis, R., Jones, I. M. and Fenouillet, E. (2003) Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion. J Biol Chem 278, 3131–6.PubMedCrossRefGoogle Scholar
  5. Basu, S., Binder, R. J., Ramalingam, T. and Srivastava, P. K. (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70 and calreticulin. Immunity 14, 303–313.PubMedCrossRefGoogle Scholar
  6. Basu, S., Binder, R. J., Suto, R., Anderson, K. M. and Srivastava, P. K. (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 12, 1539–46.PubMedCrossRefGoogle Scholar
  7. Basu, S. and Srivastava, P. K. (1999) Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity. J Exp Med 189, 797–802.PubMedCrossRefGoogle Scholar
  8. Bausinger, H., Lipsker, D., Ziylan, U., Manie, S., Briand, J. P., Cazenave, J. P., Muller, S., Haeuw, J. F., Ravanat, C., de la Salle, H. and Hanau, D. (2002) Endotoxin-free heat-shock protein 70 fails to induce APC activation. Eur. J. Immunol. 32, 3708–13.PubMedCrossRefGoogle Scholar
  9. Becker, T., Hartl, F. U. and Wieland, F. (2002) CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol 158, 1277–85.PubMedCrossRefGoogle Scholar
  10. Benvenuti, F., Lagaudriere-Gesbert, C., Grandjean, I., Jancic, C., Hivroz, C., Trautmann, A., Lantz, O. and Amigorena, S. (2004) Dendritic cell maturation controls adhesion, synapse formation, and the duration of the interactions with naive T lymphocytes. J Immunol 172, 292–301.PubMedGoogle Scholar
  11. Berwin, B., Hart, J. P., Rice, S., Gass, C., Pizzo, S. V., Post, S. R. and Nicchitta, C. V. (2003) Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. Embo J 22, 6127–36.PubMedCrossRefGoogle Scholar
  12. Binder, R. J., Han, D. K. and Srivastava, P. K. (2000) CD91: a receptor for heat shock protein gp96. Nat. Immunol. 1, 151–155.PubMedCrossRefGoogle Scholar
  13. Blachere, N. E., Li, Z., Chandawarkar, R. Y., Suto, R., Jaikaria, N. S., Basu, S., Udono, H. and Srivastava, P. K. (1997) Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med 186, 1315–22.PubMedCrossRefGoogle Scholar
  14. Boice, J. A. and Hightower, L. E. (1997) A mutational study of the peptide-binding domain of Hsc70 guided by secondary structure prediction. J Biol Chem 272, 24825–31.PubMedCrossRefGoogle Scholar
  15. Castellino, F., Boucher, P. E., Eichelberg, K., Mayhew, M., Rothman, J. E., Houghton, A. N. and Germain, R. N. (2000) Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways. J Exp Med 191, 1957–64.PubMedCrossRefGoogle Scholar
  16. Chen, X., Zeng, Y., Li, G., Larmonier, N., Graner, M. W. and Katsanis, E. (2006) Peritransplantation vaccination with chaperone-rich cell lysate induces antileukemia immunity. Biol Blood Marrow Transplant 12, 275–83.PubMedCrossRefGoogle Scholar
  17. Ciupitu, A. M., Petersson, M., O’Donnell, C. L., Williams, K., Jindal, S., Kiessling, R. and Welsh, R. M. (1998) Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity and specific cytotoxic T lymphocytes. J Exp Med 187, 685–91.PubMedCrossRefGoogle Scholar
  18. Delneste, Y., Magistrelli, G., Gauchat, J., Haeuw, J., Aubry, J., Nakamura, K., Kawakami-Honda, N., Goetsch, L., Sawamura, T., Bonnefoy, J. and Jeannin, P. (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17, 353–62.PubMedCrossRefGoogle Scholar
  19. Echchakir, H., Mami-Chouaib, F., Vergnon, I., Baurain, J. F., Karanikas, V., Chouaib, S. and Coulie, P. G. (2001) A point mutation in the alpha-actinin-4 gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human lung carcinoma. Cancer Res 61, 4078–83.PubMedGoogle Scholar
  20. Fourie, A. M., Sambrook, J. F. and Gething, M. J. (1994) Common and divergent peptide binding specificities of hsp70 molecular chaperones. J Biol Chem 269, 30470–8.PubMedGoogle Scholar
  21. Galazka, G., Stasiolek, M., Walczak, A., Jurewicz, A., Zylicz, A., Brosnan, C. F., Raine, C. S. and Selmaj, K. W. (2006) Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis. Journal of Immunology 176, 1588–99.Google Scholar
  22. Gamer, J., Multhaup, G., Tomoyasu, T., McCarty, J. S., Rudiger, S., Schonfeld, H. J., Schirra, C., Bujard, H. and Bukau, B. (1996) A cycle of binding and release of the DnaK, DnaJ and GrpE chaperones regulates activity of the Escherichia coli heat shock transcription factor sigma32. Embo J 15, 607–17.PubMedGoogle Scholar
  23. Gao, B. and Tsan, M. F. (2003) Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor alpha release by murine macrophages. J. Biol. Chem. 278, 174–9.PubMedCrossRefGoogle Scholar
  24. Gething, M. J. and Sambrook, J. (1992) Protein folding in the cell. Nature 355, 33–45.PubMedCrossRefGoogle Scholar
  25. Gordon, N. F. and Clark, B. L. (2004) The challenges of bringing autologous HSP-based vaccines to commercial reality. Methods 32, 63–9.PubMedCrossRefGoogle Scholar
  26. Graner, M., Raymond, A., Akporiaye, E. and Katsanis, E. (2000a) Tumor-derived multiple chaperone enrichment by free-solution isoelectric focusing yields potent antitumor vaccines. Cancer Immunol Immunother 49, 476–84.CrossRefGoogle Scholar
  27. Graner, M., Raymond, A., Romney, D., He, L., Whitesell, L. and Katsanis, E. (2000b) Immunoprotective activities of multiple chaperone proteins isolated from murine B-cell leukemia/lymphoma. Clin Cancer Res 6, 909–15.Google Scholar
  28. Graner, M. W. and Bigner, D. D. (2005) Chaperone proteins and brain tumors: potential targets and possible therapeutics. Neuro-oncol 7, 260–78.PubMedCrossRefGoogle Scholar
  29. Graner, M. W., Likhacheva, A., Davis, J., Raymond, A., Brandenberger, J., Romanoski, A., Thompson, S., Akporiaye, E. and Katsanis, E. (2004) Cargo from tumor-expressed albumin inhibits T-cell activation and responses. Cancer Res 64, 8085–92.PubMedCrossRefGoogle Scholar
  30. Graner, M. W., Zeng, Y., Feng, H. and Katsanis, E. (2003) Tumor-derived chaperone-rich cell lysates are effective therapeutic vaccines against a variety of cancers. Cancer Immunol Immunother 52, 226–34.PubMedGoogle Scholar
  31. Gross, C., Hansch, D., Gastpar, R. and Multhoff, G. (2003) Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol Chem 384, 267–79.PubMedCrossRefGoogle Scholar
  32. Gullo, C. A. and Teoh, G. (2004) Heat shock proteins: to present or not, that is the question. Immunol Lett 94, 1–10.PubMedCrossRefGoogle Scholar
  33. Hassen, W., El Golli, E., Baudrimont, I., Mobio, A. T., Ladjimi, M. M., Creppy, E. E. and Bacha, H. (2005) Cytotoxicity and Hsp 70 induction in Hep G2 cells in response to zearalenone and cytoprotection by sub-lethal heat shock. Toxicology 207, 293–301.PubMedCrossRefGoogle Scholar
  34. Hogan, K. T., Coppola, M. A., Gatlin, C. L., Thompson, L. W., Shabanowitz, J., Hunt, D. F., Engelhard, V. H., Ross, M. M. and Slingluff, C. L., Jr. (2004) Identification of novel and widely expressed cancer/testis gene isoforms that elicit spontaneous cytotoxic T-lymphocyte reactivity to melanoma. Cancer Res 64, 1157–63.PubMedCrossRefGoogle Scholar
  35. Hoos, A., Levey, D. L. and Lewis, J. J. (2004) Autologous heat shock protein-peptide complexes for vaccination against cancer: from bench to bedside. Dev Biol (Basel) 116, 109–15; discussion 133–43.Google Scholar
  36. Ishii, T., Udono, H., Yamano, T., Ohta, H., Uenaka, A., Ono, T., Hizuta, A., Tanaka, N., Srivastava, P. K. and Nakayama, E. (1999) Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. J Immunol 162, 1303–9.PubMedGoogle Scholar
  37. Janetzki, S., Blachere, N. E. and Srivastava, P. K. (1998) Generation of tumor-specific cytotoxic T lymphocytes and memory T cells by immunization with tumor-derived heat shock protein gp96. J. Immunother. 21, 269–76.PubMedCrossRefGoogle Scholar
  38. Javid, B., MacAry, P. A., Oehlmann, W., Singh, M. and Lehner, P. J. (2004) Peptides complexed with the protein HSP70 generate efficient human cytolytic T-lymphocyte responses. Biochem Soc Trans 32, 622–5.PubMedCrossRefGoogle Scholar
  39. Kleinjung, T., Arndt, O., Feldmann, H. J., Bockmuhl, U., Gehrmann, M., Zilch, T., Pfister, K., Schonberger, J., Marienhagen, J., Eilles, C., Rossbacher, L. and Multhoff, G. (2003) Heat shock protein 70 (Hsp70) membrane expression on head-and-neck cancer biopsy-a target for natural killer (NK) cells. Int J Radiat Oncol Biol Phys 57, 820–6.PubMedCrossRefGoogle Scholar
  40. Kupiec-Weglinski, J. W., Austyn, J. M. and Morris, P. J. (1988) Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues. J Exp Med 167, 632–45.PubMedCrossRefGoogle Scholar
  41. Kuppner, M. C., Gastpar, R., Gelwer, S., Noessner, E., Ochmann, O., Scharner, A. and Issels, R. D. (2001) The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70 induces the maturation of immature dentritic cells but reduces DC differentiation from monocyte precursors. Eur. J. Immunol. 31, 1602–1609.PubMedCrossRefGoogle Scholar
  42. Li, Z., Menoret, A. and Srivastava, P. (2002) Roles of heat-shock proteins in antigen presentation and cross-presentation. Curr Opin Immunol 14, 45–51.PubMedCrossRefGoogle Scholar
  43. Linderoth, N. A., Simon, M. N., Rodionova, N. A., Cadene, M., Laws, W. R., Chait, B. T. and Sastry, S. (2001) Biophysical analysis of the endoplasmic reticulum-resident chaperone/heat shock protein gp96/GRP94 and its complex with peptide antigen. Biochemistry 40, 1483–95.PubMedCrossRefGoogle Scholar
  44. MacAry, P. A., Javid, B., Floto, R. A., Smith, K. G., Oehlmann, W., Singh, M. and Lehner, P. J. (2004) HSP70 peptide binding mutants separate antigen delivery from dendritic cell stimulation. Immunity 20, 95–106.PubMedCrossRefGoogle Scholar
  45. Matzinger, P. and Bevan, M. J. (1977) Hypothesis: why do so many lymphocytes respond to major histocompatibility antigens? Cell Immunol 29, 1–5.PubMedCrossRefGoogle Scholar
  46. Mayer, M. P., Schroder, H., Rudiger, S., Paal, K., Laufen, T. and Bukau, B. (2000) Multistep mechanism of substrate binding determines chaperone activity of Hsp70. Nat Struct Biol 7, 586–93.PubMedCrossRefGoogle Scholar
  47. Maytin, E. V. (1992) Differential effects of heat shock and UVB light upon stress protein expression in epidermal keratinocytes. J Biol Chem 267, 23189–96.PubMedGoogle Scholar
  48. Menoret, A. (2004) Purification of recombinant and endogenous HSP70s. Methods 32, 7–12.PubMedCrossRefGoogle Scholar
  49. Minev, B. R. (2003) Technology evaluation: HSPPC-96, antigenics. Curr Opin Mol Ther 5, 680–7.PubMedGoogle Scholar
  50. Nicchitta, C. V. (2003) Re-evaluating the role of heat-shock protein-peptide interactions in tumour immunity. Nat Rev Immunol 3, 427–32.PubMedCrossRefGoogle Scholar
  51. Nicchitta, C. V. and Reed, R. C. (2000) The immunological properties of endoplasmic reticulum chaperones: a conflict of interest? Essays in Biochemistry 36, 15–25.PubMedGoogle Scholar
  52. Nieland, T. J., Tan, M. C., Monne-van Muijen, M., Koning, F., Kruisbeek, A. M. and van Bleek, G. M. (1996) Isolation of an immunodominant viral peptide that is endogenously bound to the stress protein GP96/GRP94. Proc Natl Acad Sci U S A 93, 6135–9.PubMedCrossRefGoogle Scholar
  53. Oglesbee, M. J., Pratt, M. and Carsillo, T. (2002) Role for heat shock proteins in the immune response to measles virus infection. Viral Immunol 15, 399–416.PubMedCrossRefGoogle Scholar
  54. Peng, P., Menoret, A. and Srivastava, P. K. (1997) Purification of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chromatography. J. Immunol. Methods 204, 13–21.PubMedCrossRefGoogle Scholar
  55. Popp, S., Packschies, L., Radzwill, N., Vogel, K. P., Steinhoff, H. J. and Reinstein, J. (2005) Structural dynamics of the DnaK-peptide complex. J Mol Biol 347, 1039–52.PubMedCrossRefGoogle Scholar
  56. Randow, F. and Seed, B. (2001) Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat Cell Biol 3, 891–6.PubMedCrossRefGoogle Scholar
  57. Reed, R. C., Berwin, B., Baker, J. P. and Nicchitta, C. V. (2003) GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production. Journal of Biological Chemistry 278, 31853–60.PubMedCrossRefGoogle Scholar
  58. Reed, R. C., Zheng, T. and Nicchitta, C. V. (2002) GRP94-associated enzymatic activities. Resolution by chromatographic fractionation. Journal of Biological Chemistry 277, 25082–9.PubMedCrossRefGoogle Scholar
  59. Richarme, G. and Kohiyama, M. (1993) Specificity of the Escherichia coli chaperone DnaK (70-kDa heat shock protein) for hydrophobic amino acids. J Biol Chem 268, 24074–7.PubMedGoogle Scholar
  60. Richter, K. and Buchner, J. (2001) Hsp90: chaperoning signal transduction. J Cell Physiol 188, 281–90.PubMedCrossRefGoogle Scholar
  61. Robert, J., Menoret, A., Basu, S., Cohen, N. and Srivastava, P. R. (2001) Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70. Eur J Immunol 31, 186–95.PubMedCrossRefGoogle Scholar
  62. Schui, D. K., Singh, L., Schneider, B., Knau, A., Hoelzer, D. and Weidmann, E. (2002) Inhibiting effects on the induction of cytotoxic T lymphocytes by dendritic cells pulsed with lysates from acute myeloid leukemia blasts. Leuk Res 26, 383–9.PubMedCrossRefGoogle Scholar
  63. Singh-Jasuja, H., Scherer, H. U., Hilf, N., Arnold-Schild, D., Rammensee, H. G., Toes, R. E. and Schild, H. (2000) The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. Eur. J. Immunol. 30, 2211–5.PubMedGoogle Scholar
  64. Spence, J., Cegielska, A. and Georgopoulos, C. (1990) Role of Escherichia coli heat shock proteins DnaK and HtpG (C62.5) in response to nutritional deprivation. J Bacteriol 172, 7157–66.PubMedGoogle Scholar
  65. Srivastava, P. (2002a) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20, 395–425.CrossRefGoogle Scholar
  66. Srivastava, P. (2002b) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2, 185–94.CrossRefGoogle Scholar
  67. Srivastava, P. K. (2006) Therapeutic cancer vaccines. Curr Opin Immunol.Google Scholar
  68. Srivastava, P. K. and Das, M. R. (1984) The serologically unique cell surface antigen of Zajdela ascitic hepatoma is also its tumor-associated transplantation antigen. Int J Cancer 33, 417–22.PubMedCrossRefGoogle Scholar
  69. Srivastava, P. K., DeLeo, A. B. and Old, L. J. (1986) Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci U S A 83, 3407–11.PubMedCrossRefGoogle Scholar
  70. Suto, R. and Srivastava, P. K. (1995) A mechanism for the specific immunogenicity of heat shock protein- chaperoned peptides. Science 269, 1585–8.PubMedCrossRefGoogle Scholar
  71. Tsan, M. F. and Gao, B. (2004) Heat shock protein and innate immunity. Cell Mol Immunol 1, 274–9.PubMedGoogle Scholar
  72. Udono, H. and Srivastava, P. K. (1993) Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med. 178, 1391–6.PubMedCrossRefGoogle Scholar
  73. Udono, H. and Srivastava, P. K. (1994) Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70. J. Immunol. 152, 5398–403.PubMedGoogle Scholar
  74. Ullrich, S. J., Robinson, E. A., Law, L. W., Willingham, M. and Appella, E. (1986) A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc Natl Acad Sci U S A 83, 3121–5.PubMedCrossRefGoogle Scholar
  75. Vabulas, R. M., Braedel, S., Hilf, N., Singh-Jasuja, H., Herter, S., Ahmad-Nejad, P., Kirschning, C. J., Da Costa, C., Rammensee, H. G., Wagner, H. and Schild, H. (2002a) The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J Biol Chem 277, 20847–53.CrossRefGoogle Scholar
  76. Vabulas, R. M., Wagner, H. and Schild, H. (2002b) Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol 270, 169–84.Google Scholar
  77. van Eden, W., Koets, A., van Kooten, P., Prakken, B. and van der Zee, R. (2003) Immunopotentiating heat shock proteins: negotiators between innate danger and control of autoimmunity. Vaccine 21, 897–901.PubMedCrossRefGoogle Scholar
  78. Wang, Y., Kelly, C. G., Karttunen, J. T., Whittall, T., Lehner, P. J., Duncan, L., MacAry, P., Younson, J. S., Singh, M., Oehlmann, W., Cheng, G., Bergmeier, L. and Lehner, T. (2001) CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 15, 971–83.PubMedCrossRefGoogle Scholar
  79. Wassenberg, J. J., Dezfulian, C. and Nicchitta, C. V. (1999) Receptor mediated and fluid phase pathways for internalization of the ER Hsp90 chaperone GRP94 in murine macrophages. J. Cell Sci. 112, 2167–75.PubMedGoogle Scholar
  80. Weidinger, G., Czub, S., Neumeister, C., Harriott, P., ter Meulen, V. and Niewiesk, S. (2000) Role of CD4(+) and CD8(+) T cells in the prevention of measles virus-induced encephalitis in mice. J Gen Virol 81, 2707–13.PubMedGoogle Scholar
  81. Wendling, U., Paul, L., van der Zee, R., Prakken, B., Singh, M. and van Eden, W. (2000) A conserved mycobacterial heat shock protein (hsp) 70 sequence prevents adjuvant arthritis upon nasal administration and induces IL-10-producing T cells that cross-react with the mammalian self-hsp70 homologue. J Immunol 164, 2711–7.PubMedGoogle Scholar
  82. Yedavelli, S. P., Guo, L., Daou, M. E., Srivastava, P. K., Mittelman, A. and Tiwari, R. K. (1999) Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model. Int J Mol Med 4, 243–8.PubMedGoogle Scholar
  83. Zabrecky, J. R. and Sawlivich, W. (2004) Purification of the heat shock protein, gp96, from natural sources. Methods 32, 3–6.PubMedCrossRefGoogle Scholar
  84. Zeng, Y., Feng, H., Graner, M. W. and Katsanis, E. (2003) Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity. Blood 101, 4485–91.PubMedCrossRefGoogle Scholar
  85. Zeng, Y., Graner, M. W., Thompson, S., Marron, M. and Katsanis, E. (2005) Induction of BCR-ABL-specific immunity following vaccination with chaperone-rich cell lysates derived from BCR-ABL+ tumor cells. Blood 105, 2016–22.PubMedCrossRefGoogle Scholar
  86. Zhu, X., Zhao, X., Burkholder, W. F., Gragerov, A., Ogata, C. M., Gottesman, M. E. and Hendrickson, W. A. (1996) Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272, 1606–14.PubMedCrossRefGoogle Scholar
  87. Zimmerman, L. H., Levine, R. A. and Farber, H. W. (1991) Hypoxia induces a specific set of stress proteins in cultured endothelial cells. J Clin Invest 87, 908–14.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Charles A Gullo
    • 1
  • Paul Macary
    • 2
  • Michael Graner
    • 3
  1. 1.Department of Clinical ResearchSingapore General HospitalSingapore
  2. 2.Immunology ProgramNational University of SingaporeSingapore
  3. 3.The Preston Robert Tisch Brain Tumor Center at Duke UniversityDuke University Medical SchoolUSA

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