Immunostimulatory functions of membrane-bound and exported heat shock protein 70.

摘要: In the search for tumor-specific antigens, microbial and eukaryotic heat shock proteins (HSP) have been identified. Intracellularly, HSPs function as molecular chaperones supporting folding transport of a great variety polypeptides under normal physiological conditions following stress stimuli. Furthermore, interferon-gamma elevated body temperature induced by exercise found to increase serum levels in humans. Extracellularly localized or plasma membrane-bound elicit potent anti-cancer immune response mediated either adaptive innate system. Following uptake HSP (HSP70 gp96)-peptide complexes antigen presenting cells (APCs) "cross-presentation" HSP-chaperoned peptides on MHC class I molecules, CD8-specific T cell is induced. Apart from chaperoning peptides, per se provide activatory signals Binding peptide-free HSP70 APCs via Toll-like receptors (TLRs) initiates secretion pro-inflammatory cytokines thus results broad non-specific immunostimulation. An unusual membrane localization Hsp70, major heat-inducible member family, tumor but not corresponding tissues was act recognition structure natural killer (NK) cells. Soluble well can directly activate cytolytic migratory capacity NK actively release HSP70s lipid vesicles with biophysical properties exosomes. These HSP70-presenting exosomes are thought stimulate system vivo. Taken together, depending their intra/extracellular localization, peptide loading status, origin route application, exert activation danger cancer immunity protect lethal damage exogenous