Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity.
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.
Blachere
N E
NE
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington 06030, USA.
Li
Z
Z
Chandawarkar
R Y
RY
Suto
R
R
Jaikaria
N S
NS
Basu
S
S
Udono
H
H
Srivastava
P K
PK
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*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C052646:sarcoma glycoprotein gp96 rejection antigens