scholarly journals CD40, an extracellular receptor for binding and uptake of Hsp70–peptide complexes

2002 ◽  
Vol 158 (7) ◽  
pp. 1277-1285 ◽  
Author(s):  
Thalia Becker ◽  
F.-Ulrich Hartl ◽  
Felix Wieland
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Function ◽  
Surface Protein ◽  
Mhc I ◽  
Peptide Complex ◽  
Exogenous Hsp70 ◽  
A Cell ◽  
Peptide Complexes ◽  
Antigen Presenting

Tumor and viral antigens elicit a potent immune response by heat shock protein–dependent uptake of antigenic peptide with subsequent presentation by MHC I. Receptors on antigen-presenting cells that specifically bind and internalize a heat shock protein–peptide complex have not yet been identified. Here, we show that cells expressing CD40, a cell surface protein crucial for B cell function and autoimmunity, specifically bind and internalize human Hsp70 with bound peptide. Binding of Hsp70–peptide complex to the exoplasmic domain of CD40 is mediated by the NH2-terminal nucleotide–binding domain of Hsp70 in its ADP state. The Hsp70 cochaperone Hip, but not the bacterial Hsp70 homologue DnaK, competes formation of the Hsp70–CD40 complex. Binding of Hsp70-ADP to CD40 is strongly increased in the presence of Hsp70 peptide substrate, and induces signaling via p38. We suggest that CD40 is a cochaperone-like receptor mediating the uptake of exogenous Hsp70–peptide complexes by macrophages and dendritic cells.

Synovial fluid-derivedYersinia-reactive T cells responding to human 65-kDa heat-shock protein and heat-stressed antigen-presenting cells

1991 ◽  
Vol 21 (9) ◽  
pp. 2139-2143 ◽  
Author(s):  
Elisabeth Hermann ◽  
Ansgar W. Lohse ◽  
Ruurd Van Der Zee ◽  
Willem Van Eden ◽  
Werner J. Mayet ◽  
...  
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Synovial Fluid ◽  
Heat Shock Protein ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

scholarly journals HEAT SHOCK PROTEIN HSP70: PREREQUISITES FOR USE AS A MEDICINAL PRODUCT

2021 ◽  
Vol 9 (5) ◽  
pp. 346-355
Author(s):  
V. M. Pokrovsky ◽  
E. A. Patrakhanov ◽  
O. V. Antsiferov ◽  
I. M. Kolesnik ◽  
A. V. Belashova ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Science Research ◽  
Literary Analysis ◽  
Protective Effects ◽  
Overwhelming Evidence ◽  
Biological Target ◽  
Exogenous Hsp70 ◽  
Heat Shock Protein Hsp70 ◽  
External Stimuli

Heat shock protein Hsp70 is one of the main cytoprotection components under the action of various external stimuli. The analysis of the literature data shows that nowadays, the researches’ overwhelming evidence has proven the role of Hsp70 as a biological target for the drug development; however, the ideas about its use as a drug are often multidirectional.The aim of the article is to analyze and generalize the literature data on the features of the physiological functions of heat shock protein Hsp 70, and indicate the possibilities of its use for the pharmacological correction of various pathological conditions.Materials and methods. In the process of selecting material for writing this review article, such databases as Google Patents, Science Research Portal, Google Scholar, ScienceDirect, CiteSeer, Publications, ResearchIndex, Ingenta, PubMed, KEGG, etc. were used The following words and word combinations were selected as markers for identifying the literature: Hsp70, Hsp70 stroke, Hsp70 neuroprotection, Hsp70 cytoprotection, recombinant drugs.Results. In this review, the pharmacology of one of the key members of this family, Hsp70, was focused on. The literary analysis confirms that this molecule is an endogenous regulator of many physiological processes and demonstrates tissue protective effects in modeling ischemic, neurodegenerative and inflammatory processes. The use of recombinant exogenous Hsp70 mimics the endogenous function of the protein, indicating the absence of a number of typical limitations characteristic of pharmacotherapy with high molecular weight compounds, such as immunogenicity, a rapid degradation by proteases, or a low penetration of histohematogenous barriers.Conclusion. Thus, Hsp70 may become a promising agent for clinical trials as a drug for the treatment of patients with neurological, immunological, and cardiovascular profiles.

Anti-tumor effect of heat shock protein 70-Peptide complexes on A-549 cells

2007 ◽  
Vol 19 (3) ◽  
pp. 210-215 ◽  
Author(s):  
Hong-qi Wang ◽  
Chen-xia Hu ◽  
Ling Hu ◽  
Wei-xi Shen ◽  
Jian Zhao ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Peptide Complexes

Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1636-1642 ◽  
Author(s):  
Ruibo Wang ◽  
Joseph T. Kovalchin ◽  
Peggy Muhlenkamp ◽  
Rajiv Y. Chandawarkar
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Mhc Class Ii ◽  
Lipid Raft ◽  
Heat Shock Protein 70 ◽  
Emerging Infections ◽  
Mhc Ii ◽  
Adaptive Immune ◽  
Exogenous Hsp70 ◽  
Bacteria And Fungi

The extracellular presence of endotoxin-free heat shock protein 70 (HSP70) enhances the rate and capacity of macrophage-mediated phagocytosis at 6 times the basal rate. It is protein-specific, dose- and time-dependent and involves the internalization of inert microspheres, Gram-positive and -negative bacteria and fungi. Structurally, exogenous HSP70 binds the macrophage plasma membrane, specifically on its lipid raft-microdomain. Disruption of lipid rafts, HSP70-LR interaction, or denaturing HSP70 abrogates the HSP-mediated increase in phagocytosis. Further, HSP70-mediated phagocytosis directly enhances the processing and presentation of internalized antigens via the endocytic MHC class-II pathway to CD4+ T lymphocytes. Modulating the HSP70-LR interaction presents an opportunity to intervene at the level of host-pathogen interface: a therapeutic tool for emerging infections, especially when conventional treatment with antibiotics is ineffective (antibiotic resistance) or unavailable (rapidly spreading, endemic). These results identify a new role for HSP70, a highly conserved molecule in stimulating phagocytosis: a primordial macrophage function, thereby influencing both innate and adaptive immune responses.

BCG (Bacille Calmette–Guérin) HspCs (heat-shock protein–peptide complexes) induce T-helper 1 responses and protect against live challenge in a murine aerosol challenge model of pulmonary tuberculosis

2004 ◽  
Vol 32 (4) ◽  
pp. 626-628 ◽  
Author(s):  
C.A.L.S. Colaco ◽  
C.R. Bailey ◽  
J. Keeble ◽  
K.B. Walker
Keyword(s):  
Heat Shock ◽  
Pulmonary Tuberculosis ◽  
Immune Responses ◽  
Heat Shock Protein ◽  
T Helper ◽  
T Helper 1 ◽  
Bacille Calmette Guerin ◽  
Vaccine Candidates ◽  
Peptide Complexes ◽  
Further Development

The need for an effective TB (tuberculosis) vaccine remains acute, with tuberculosis still one of the major killers worldwide and 3 million new infections annually. We report here on the immune responses elicited by HspCs (heat-shock protein–peptide complexes) isolated from BCG (Bacille Calmette–Guérin) vaccine. These HspCs elicit both the appropriate cellular and protective immune responses required to merit their further development as TB vaccine candidates.

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