Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity

Nathalie E. Blachere, Zihai Li, Rajiv Y. Chandawarkar, Ryuichiro Suto, Navdeep S. Jaikaria, Sreyashi Basu, Heiichiro Udono, Praniod K. Srivastava

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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.

Original languageEnglish
Pages (from-to)1315-1322
Number of pages8
JournalJournal of Experimental Medicine
Volume186
Issue number8
DOIs
Publication statusPublished - Oct 20 1997

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Cytotoxic T-Lymphocytes
Heat-Shock Proteins
Immunity
Peptides
Neoplasms
Viruses
T-Lymphocytes
In Vitro Techniques
Macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. / Blachere, Nathalie E.; Li, Zihai; Chandawarkar, Rajiv Y.; Suto, Ryuichiro; Jaikaria, Navdeep S.; Basu, Sreyashi; Udono, Heiichiro; Srivastava, Praniod K.

In: Journal of Experimental Medicine, Vol. 186, No. 8, 20.10.1997, p. 1315-1322.

Research output: Contribution to journalArticle

Blachere, Nathalie E. ; Li, Zihai ; Chandawarkar, Rajiv Y. ; Suto, Ryuichiro ; Jaikaria, Navdeep S. ; Basu, Sreyashi ; Udono, Heiichiro ; Srivastava, Praniod K. / Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. In: Journal of Experimental Medicine. 1997 ; Vol. 186, No. 8. pp. 1315-1322.
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