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 +7 more
Reads0
Chats0
TLDR
It is demonstrated that HSPs are CD8+ T cell response–eliciting adjuvants that are immunologically active, as tested by their ability to elicit antitumor immunity and specificCD8+ cytolytic T lymphocyte response.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.read more
Citations
More filters
Journal ArticleDOI
Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery.
William B. Pratt,David O. Toft +1 more
TL;DR: This purified system of five purified proteins should facilitate understanding of how eukaryotlc hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
Journal ArticleDOI
CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin.
TL;DR: It is shown here that complexes of peptides with heat shock proteins hsp90, calreticulin, and hsp70 are also taken up by macrophages and dendritic cells and re-presented by MHC class I molecules.
Journal ArticleDOI
Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.
Clotilde Théry,Armelle Regnault,Jérôme Garin,Joseph Wolfers,Laurence Zitvogel,Paola Ricciardi-Castagnoli,Graça Raposo,Sebastian Amigorena +7 more
TL;DR: DC-derived exosomes accumulate a defined subset of cellular proteins reflecting their endosomal biogenesis and accounting for their biological function, and exosome production is downregulated upon DC maturation, indicating that in vivo,Exosomes are produced by immature DCs in peripheral tissues.
Journal ArticleDOI
Roles of heat-shock proteins in innate and adaptive immunity
TL;DR: The immunological properties of HSPs enable them to be used in new immunotherapies of cancers and infections and make them uniquely suited to an important role in organismal survival by their participation in innate and adaptive immune responses.
Journal ArticleDOI
The 90-kDa molecular chaperone family : structure, function, and clinical applications. A comprehensive review
TL;DR: The present review summarizes the current knowledge about the cellular functions, expression, and clinical implications of the 90-kDa molecular chaperone family and some approaches for future research.
References
More filters
Journal ArticleDOI
MHC ligands and peptide motifs: first listing.
TL;DR: A compendium of major histocompatibility complex (MHC) peptide motifs and MHC ligands known to date, together with a discussion of the methods used to gain this information, is provided.
Journal ArticleDOI
Structural Analysis of Substrate Binding by the Molecular Chaperone DnaK
Xiaotian Zhu,Xun Zhao,William F. Burkholder,Alexander Gragerov,Craig M. Ogata,Max E. Gottesman,Wayne A. Hendrickson +6 more
TL;DR: The crystal structure of a peptide complex with the substrate-binding unit of DnaK has been determined at 2.0 Å resolution, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.
Journal ArticleDOI
A Mechanism for the Specific Immunogenicity of Heat Shock Protein-Chaperoned Peptides
TL;DR: It is shown that exogenous antigens chaperoned by a heat shockprotein can be channeled into the endogenous pathway, presented by MHC class I molecules, and recognized by CD8+ T lymphocytes, which provides a basis for the tumor-specific and virus-specific immunogenicity of cognate heat shock protein preparations and offer a mechanism for the classical phenomenon of cross-priming.
Journal ArticleDOI
Peptide binding and release by proteins implicated as catalysts of protein assembly
TL;DR: Short hydrophilic synthetic peptides have been tested as possible mimics of polypeptide chain substrates to help define an enzymatic basis for these activities of protein folding and assembly processes.
Journal ArticleDOI
Heat shock protein 70-associated peptides elicit specific cancer immunity.
TL;DR: The data indicate that antigenicity of hSp70 preparations derives, not from hsp70 per se, but from associated peptides, which may suggest a novel method of using the peptide-binding property of hSP70 for specific vaccination against cancer and infectious diseases.