title: Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity.
abstract: Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP-peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP-peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96- peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response-eliciting adjuvants.
authors.affiliation: Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington 06030, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Blachere
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: R Y
authors.initials: RY
authors.lastname: Chandawarkar
authors.forename: R
authors.initials: R
authors.lastname: Suto
authors.forename: N S
authors.initials: NS
authors.lastname: Jaikaria
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: H
authors.initials: H
authors.lastname: Udono
authors.forename: P K
authors.initials: PK
authors.lastname: Srivastava
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013945:Thymoma; D013953:Thymus Neoplasms; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C052646:sarcoma glycoprotein gp96 rejection antigens