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10.1074/jbc.M115.695304 http://scihub22266oqcxt.onion/10.1074/jbc.M115.695304 C4861462!4861462!26719339     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2016 ; 291 (17): 8931-50 Nephropedia Template TP {{tp|p=26719339|t=2016. Configuration-dependent Presentation of Multivalent IL-15:IL-15R? Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity* |pdf=|usr=}}{{26719339}} gab.com Text Configuration-dependent Presentation of Multivalent IL-15:IL-15R Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity* JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=26719339 #FOAvip Here we report a ?configuration-dependent? mechanism of action for IL-15:IL-15R? (heterodimeric IL-15 or hetIL-15) where the manner by which IL-15:IL-15R? molecules are presented to target cells significantly affects its function as a vaccine adjuvant. Although the cellular mechanism of IL-15 trans-presentation via IL-15R? and its importance for IL-15 function have been described, the full effect of the IL-15:IL-15R? configuration on responding cells is not yet known. We found that trans-presenting IL-15:IL-15R? in a multivalent fashion on the surface of antigen-encapsulating nanoparticles enhanced the ability of nanoparticle-treated dendritic cells (DCs) to stimulate antigen-specific CD8+ T cell responses. Localization of multivalent IL-15:IL-15R? and encapsulated antigen to the same DC led to maximal T cell responses. Strikingly, DCs incubated with IL-15:IL-15R?-coated nanoparticles displayed higher levels of functional IL-15 on the cell surface, implicating a mechanism for nanoparticle-mediated transfer of IL-15 to the DC surface. Using artificial antigen-presenting cells to highlight the effect of IL-15 configuration on DCs, we showed that artificial antigen-presenting cells presenting IL-15:IL-15R? increased the sensitivity and magnitude of the T cell response, whereas IL-2 enhanced the T cell response only when delivered in a paracrine fashion. Therefore, the mode of cytokine presentation (configuration) is important for optimal immune responses. We tested the effect of configuration dependence in an aggressive model of murine melanoma and demonstrated significantly delayed tumor progression induced by IL-15:IL-15R?-coated nanoparticles in comparison with monovalent IL-15:IL-15R?. The novel mechanism of IL-15 transfer to the surface of antigen-processing DCs may explain the enhanced potency of IL-15:IL-15R?-coated nanoparticles for antigen delivery. Twit Text FOAVip Configuration-dependent Presentation of Multivalent IL-15:IL-15R Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity* ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=26719339 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26719339 #FOAvip English Wikipedia <ref>{{Cite pmid|26719339}}</ref> Configuration-dependent Presentation of Multivalent IL-15:IL-15R? Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity* #MMPMID26719339 Hong E; Usiskin IM; Bergamaschi C; Hanlon DJ; Edelson RL; Justesen S; Pavlakis GN; Flavell RA; Fahmy TM J Biol Chem 2016[Apr]; 291 (17): 8931-50 PMID26719339show ga Here we report a ?configuration-dependent? mechanism of action for IL-15:IL-15R? (heterodimeric IL-15 or hetIL-15) where the manner by which IL-15:IL-15R? molecules are presented to target cells significantly affects its function as a vaccine adjuvant. Although the cellular mechanism of IL-15 trans-presentation via IL-15R? and its importance for IL-15 function have been described, the full effect of the IL-15:IL-15R? configuration on responding cells is not yet known. We found that trans-presenting IL-15:IL-15R? in a multivalent fashion on the surface of antigen-encapsulating nanoparticles enhanced the ability of nanoparticle-treated dendritic cells (DCs) to stimulate antigen-specific CD8+ T cell responses. Localization of multivalent IL-15:IL-15R? and encapsulated antigen to the same DC led to maximal T cell responses. Strikingly, DCs incubated with IL-15:IL-15R?-coated nanoparticles displayed higher levels of functional IL-15 on the cell surface, implicating a mechanism for nanoparticle-mediated transfer of IL-15 to the DC surface. Using artificial antigen-presenting cells to highlight the effect of IL-15 configuration on DCs, we showed that artificial antigen-presenting cells presenting IL-15:IL-15R? increased the sensitivity and magnitude of the T cell response, whereas IL-2 enhanced the T cell response only when delivered in a paracrine fashion. Therefore, the mode of cytokine presentation (configuration) is important for optimal immune responses. We tested the effect of configuration dependence in an aggressive model of murine melanoma and demonstrated significantly delayed tumor progression induced by IL-15:IL-15R?-coated nanoparticles in comparison with monovalent IL-15:IL-15R?. The novel mechanism of IL-15 transfer to the surface of antigen-processing DCs may explain the enhanced potency of IL-15:IL-15R?-coated nanoparticles for antigen delivery. äConfiguration-dependent Presentation of Multivalent IL-15:IL-15R? Enha(epmc).pdf DeepDyve Pubget Overpricing