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,*
*
First Department of Surgery and
Department of Parasitology and Immunology, Okayama University Medical School, Okayama, Japan;
Department of Medical Zoology and Immunology, Nagasaki University School of Medicine, Nagasaki, Japan;
§
Department of Microbiology, Okayama University Dental School, Okayama, Japan; and
¶
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030
We have previously demonstrated that vaccination with heat shock
proteins hsp70, hsp90, and gp96 elicits specific immunity against the
tumor from which the hsps were purified. Although the association of
tumor Ag peptides with these hsps have been suggested, the
identification of the peptides or their precursors stripped from the
hsps remained to be resolved. We show in this report that an
Ld-restricted cytotoxic T lymphocyte epitope of a mouse
leukemia RL
1 and its precursors are associated with the chaperones
hsp90 and hsp70 in the cytosol and gp96 in the lumen of the endoplasmic
reticulum. Hsp70 was associated with only final sized octamer, while
hsp90 was found to associate with the octamer and two distinct
precursor peptides. The gp96 was associated with the octamer and one of
the two precursors. Thus, each of the hsps bound a distinct set of
peptides. Our results have demonstrated for the first time that the
hsps associate not only with final sized tumor Ag peptide but also with
its precursors. The implication of this evidence is also discussed in
terms of the roles of hsps in MHC class I Ag
processing/presentation.
This article has been cited by other articles:
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R. Dressel, C. Grzeszik, M. Kreiss, D. Lindemann, T. Herrmann, L. Walter, and E. Gunther Differential Effect of Acute and Permanent Heat Shock Protein 70 Overexpression in Tumor Cells on Lysability by Cytotoxic T Lymphocytes Cancer Res., December 1, 2003; 63(23): 8212 - 8220. [Abstract] [Full Text] [PDF]
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R. Schirmbeck, N. Fissolo, P. Chaplin, and J. Reimann Enhanced Priming of Multispecific, Murine CD8+ T Cell Responses by DNA Vaccines Expressing Stress Protein-Binding Polytope Peptides J. Immunol., August 1, 2003; 171(3): 1240 - 1246. [Abstract] [Full Text] [PDF]
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Y. Zeng, H. Feng, M. W. Graner, and E. Katsanis Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity Blood, June 1, 2003; 101(11): 4485 - 4491. [Abstract] [Full Text] [PDF]
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X.-Y. Wang, X. Chen, M. H. Manjili, E. Repasky, R. Henderson, and J. R. Subjeck Targeted Immunotherapy Using Reconstituted Chaperone Complexes of Heat Shock Protein 110 and Melanoma-associated Antigen gp100 Cancer Res., May 15, 2003; 63(10): 2553 - 2560. [Abstract] [Full Text] [PDF]
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H. Cwiklinska, M. P. Mycko, O. Luvsannorov, B. Walkowiak, C. F. Brosnan, C. S. Raine, and K. W. Selmaj Heat shock protein 70 associations with myelin basic protein and proteolipid protein in multiple sclerosis brains Int. Immunol., February 1, 2003; 15(2): 241 - 249. [Abstract] [Full Text] [PDF]
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W. J. Cho, W. J. Yoon, C. H. Moon, S. J. Cha, H. Song, H. R. Cho, S. J. Jang, D. K. Chung, C. S. Jeong, and J. W. Park Molecular Cloning of a Novel Chaperone-like Protein Induced by Rhabdovirus Infection with Sequence Similarity to the Bacterial Extracellular Solute-binding Protein Family 5 J. Biol. Chem., October 25, 2002; 277(44): 41489 - 41496. [Abstract] [Full Text] [PDF]
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 F. Belli, A. Testori, L. Rivoltini, M. Maio, G. Andreola, M. R. Sertoli, G. Gallino, A. Piris, A. Cattelan, I. Lazzari, et al. Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings J. Clin. Oncol., October 15, 2002; 20(20): 4169 - 4180. [Abstract] [Full Text] [PDF]
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P. P. Banerjee, D. S. Vinay, A. Mathew, M. Raje, V. Parekh, D. V. R. Prasad, A. Kumar, D. Mitra, and G. C. Mishra Evidence That Glycoprotein 96 (B2), a Stress Protein, Functions as a Th2-Specific Costimulatory Molecule J. Immunol., October 1, 2002; 169(7): 3507 - 3518. [Abstract] [Full Text] [PDF]
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T. Huang, H. Deng, A. W. Wolkoff, and R. J. Stockert Phosphorylation-dependent Interaction of the Asialoglycoprotein Receptor with Molecular Chaperones J. Biol. Chem., September 27, 2002; 277(40): 37798 - 37803. [Abstract] [Full Text] [PDF]
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M. K. Callahan, D. Chaillot, C. Jacquin, P. R. Clark, and A. Menoret Differential Acquisition of Antigenic Peptides by Hsp70 and Hsc70 under Oxidative Conditions J. Biol. Chem., September 6, 2002; 277(37): 33604 - 33609. [Abstract] [Full Text] [PDF]
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 A. Michils, D. Dutry, V. Z. de Beyl, M. Remmelink, V. de Maertelaer, and P. Rocmans Peripheral Blood Mononuclear Cell Proliferation to Heat Shock Protein-70 Derived from Autologous Lung Carcinoma Am. J. Respir. Crit. Care Med., September 1, 2002; 166(5): 749 - 753. [Abstract] [Full Text] [PDF]
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 T. Yamano, S. Murata, N. Shimbara, N. Tanaka, T. Chiba, K. Tanaka, K. Yui, and H. Udono Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing J. Exp. Med., July 15, 2002; 196(2): 185 - 196. [Abstract] [Full Text] [PDF]
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A.-M. Sponaas, U. Zuegel, S. Weber, R. Hurwitz, R. Winter, S. Lamer, P. R. Jungblut, and S. H. E. Kaufmann Immunization with gp96 from Listeria monocytogenes-Infected Mice Is Due to N-Formylated Listerial Peptides J. Immunol., December 1, 2001; 167(11): 6480 - 6486. [Abstract] [Full Text] [PDF]
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Y. Kawarada, R. Ganss, N. Garbi, T. Sacher, B. Arnold, and G. J. Hammerling NK- and CD8+ T Cell-Mediated Eradication of Established Tumors by Peritumoral Injection of CpG-Containing Oligodeoxynucleotides J. Immunol., November 1, 2001; 167(9): 5247 - 5253. [Abstract] [Full Text] [PDF]
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H. Udono, T. Yamano, Y. Kawabata, M. Ueda, and K. Yui Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70 Int. Immunol., October 1, 2001; 13(10): 1233 - 1242. [Abstract] [Full Text] [PDF]
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 U. Zugel, A.-M. Sponaas, J. Neckermann, B. Schoel, and S. H. E. Kaufmann gp96-Peptide Vaccination of Mice against Intracellular Bacteria Infect. Immun., June 1, 2001; 69(6): 4164 - 4167. [Abstract] [Full Text] [PDF]
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C. Castelli, A.-M. T. Ciupitu, F. Rini, L. Rivoltini, A. Mazzocchi, R. Kiessling, and G. Parmiani Human Heat Shock Protein 70 Peptide Complexes Specifically Activate Antimelanoma T Cells Cancer Res., January 1, 2001; 61(1): 222 - 227. [Abstract] [Full Text]
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X.-Y. Wang, L. Kazim, E. A. Repasky, and J. R. Subjeck Characterization of Heat Shock Protein 110 and Glucose-Regulated Protein 170 as Cancer Vaccines and the Effect of Fever-Range Hyperthermia on Vaccine Activity J. Immunol., January 1, 2001; 166(1): 490 - 497. [Abstract] [Full Text] [PDF]
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D. K. Vanaja, M. E. Grossmann, E. Celis, and C. Y. F. Young Tumor Prevention and Antitumor Immunity with Heat Shock Protein 70 Induced by 15-Deoxy-{{Delta}}12,14-prostaglandin J2 in Transgenic Adenocarcinoma of Mouse Prostate Cells Cancer Res., September 1, 2000; 60(17): 4714 - 4718. [Abstract] [Full Text]
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N. A. Linderoth, A. Popowicz, and S. Sastry Identification of the Peptide-binding Site in the Heat Shock Chaperone/Tumor Rejection Antigen gp96 (Grp94) J. Biol. Chem., February 25, 2000; 275(8): 5472 - 5477. [Abstract] [Full Text] [PDF]
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Y. Goldman, A. Peled, and M. Shinitzky Effective Elimination of Lung Metastases Induced by Tumor Cells Treated with Hydrostatic Pressure and N-Acetyl-L-Cysteine Cancer Res., January 1, 2000; 60(2): 350 - 358. [Abstract] [Full Text]
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S. Basu and P. K. Srivastava Calreticulin, a Peptide-binding Chaperone of the Endoplasmic Reticulum, Elicits Tumor- and Peptide-specific Immunity J. Exp. Med., March 1, 1999; 189(5): 797 - 802. [Abstract] [Full Text] [PDF]
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M. F. N. Rosser and C. V. Nicchitta Ligand Interactions in the Adenosine Nucleotide-binding Domain of the Hsp90 Chaperone, GRP94. I. EVIDENCE FOR ALLOSTERIC REGULATION OF LIGAND BINDING J. Biol. Chem., July 21, 2000; 275(30): 22798 - 22805. [Abstract] [Full Text] [PDF]
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N. A. Linderoth, M. N. Simon, J. F. Hainfeld, and S. Sastry Binding of Antigenic Peptide to the Endoplasmic Reticulum-resident Protein gp96/GRP94 Heat Shock Chaperone Occurs in Higher Order Complexes. ESSENTIAL ROLE OF SOME AROMATIC AMINO ACID RESIDUES IN THE PEPTIDE-BINDING SITE J. Biol. Chem., March 30, 2001; 276(14): 11049 - 11054. [Abstract] [Full Text] [PDF]
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R. J. Binder, N. E. Blachere, and P. K. Srivastava Heat Shock Protein-chaperoned Peptides but Not Free Peptides Introduced into the Cytosol Are Presented Efficiently by Major Histocompatibility Complex I Molecules J. Biol. Chem., May 11, 2001; 276(20): 17163 - 17171. [Abstract] [Full Text] [PDF]
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