Responses of peptide-specific T cells to stimulation with polystyrene beads carrying HLA class I molecules loaded with single peptides

Chersi, Alberto; Galati, Rossella; Accapezzato, Daniele; Francavilla, Vittorio; Barnaba, Vincenzo; Butler, Richard H.; Tanigaki, Nobuyuki

doi:10.1016/j.jim.2004.05.001

Cited by 2 publications

(3 citation statements)

References 24 publications

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“…The dissociation of preformed pMHC-I complexes and replacement of high-affinity peptides were performed as previously described (31). Peptide-pulsed cells were stained with mAb W6/32 and analyzed by flow cytometry, or used as target cells for NK cell degranulation assay.…”

Section: Peptide Loading On Mhc Class I Moleculesmentioning

confidence: 99%

ERAP1 Regulates Natural Killer Cell Function by Controlling the Engagement of Inhibitory Receptors

et al. 2015

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The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by MHC class I (MHC-I) molecules. Herein, we demonstrate that genetic or pharmacological inhibition of ERAP1 on human tumor cell lines perturbs their ability to engage several classes of inhibitory receptors by their specific ligands, including killer cell Ig-like receptors (KIR) by classical MHC-I-peptide (pMHC-I) complexes and the lectin-like receptor CD94-NKG2A by nonclassical pMHC-I complexes, in each case leading to natural killer (NK) cell killing. The protective effect of pMHC-I complexes could be restored in ERAP1-deficient settings by the addition of known high-affinity peptides, suggesting that ERAP1 was needed to positively modify the affinity of natural ligands. Notably, ERAP1 inhibition enhanced the ability of NK cells to kill freshly established human lymphoblastoid cell lines from autologous or allogeneic sources, thereby promoting NK cytotoxic activity against target cells that would not be expected because of KIR-KIR ligand matching. Overall, our results identify ERAP1 as a modifier to leverage immune functions that may improve the efficacy of NK cellbased approaches for cancer immunotherapy.

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Section: Peptide Loading On Mhc Class I Moleculesmentioning

confidence: 99%

ERAP1 Regulates Natural Killer Cell Function by Controlling the Engagement of Inhibitory Receptors

et al. 2015

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“…Several methods have been developed to increase recombinant protein presentation via the MHC I pathway including genetically modifying bacterial toxins to possess CTL epitopes, fusion of antigens with heat shock proteins, and adsorbing proteins on the surface of iron oxide or polystyrene beads. , Delivery of proteins in particles capable of being phagocytosed by antigen presenting cells represents a robust method of generating CTL responses against any recombinant protein. Expanding on earlier work done on conjugating proteins to insoluble carriers, we have developed acid-labile particles that encapsulate proteins in a cross-linked polyacrylamide-based hydrogel. − Upon phagocytosis, these particles quickly degrade under the acidic conditions found in endo- and lysosomal compartments, resulting in the release of the encapsulated protein.…”

Section: Introductionmentioning

confidence: 99%

“…Several methods have been developed to increase recombinant protein presentation via the MHC I pathway including genetically modifying bacterial toxins to possess CTL epitopes, 6 fusion of antigens with heat shock proteins, 7 and adsorbing proteins on the surface of iron oxide or polystyrene beads. 8,9 Delivery of proteins in particles capable of being phagocytosed by antigen presenting cells represents a robust method of generating CTL responses against any recombinant protein. Expanding on earlier work done on conjugating proteins to insoluble carriers, we have developed acid-labile particles that encapsulate proteins in a cross-linked polyacrylamide-based hydrogel.…”

Section: Introductionmentioning

confidence: 99%

Acid-Degradable Polyurethane Particles for Protein-Based Vaccines: Biological Evaluation and in Vitro Analysis of Particle Degradation Products

et al. 2008

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Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a polyurethane with acetal moieties embedded throughout the polymer, and characterized by dynamic light scattering and transmission electron microscopy. The small molecule degradation by-product of the particles was synthesized and tested in vitro for toxicity indicating an LC50 of 12,500 μg/ml. A new liquid chromatography-mass spectrometry technique was developed to monitor the in vitro degradation of these particles. The degradation by-product inside RAW macrophages was at its highest level after 24 hours of culture and was efficiently exocytosed until it was no longer detectable after four days. When tested in vitro, these particles induced a substantial increase in the presentation of the immunodominant ovalbumin-derived peptide SIINFEKL in both macrophages and dendritic cells. In addition, vaccination with these particles generated a cytotoxic T-lymphocyte response that was superior to both free ovalbumin and particles made from an analogous but slower-degrading acid-labile polyurethane polymer. Overall, we present a fully degradable polymer system with non-toxic by-products, which may find use in various biomedical applications including protein-based vaccines.

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Responses of peptide-specific T cells to stimulation with polystyrene beads carrying HLA class I molecules loaded with single peptides

Cited by 2 publications

References 24 publications

ERAP1 Regulates Natural Killer Cell Function by Controlling the Engagement of Inhibitory Receptors

ERAP1 Regulates Natural Killer Cell Function by Controlling the Engagement of Inhibitory Receptors

Acid-Degradable Polyurethane Particles for Protein-Based Vaccines: Biological Evaluation and in Vitro Analysis of Particle Degradation Products

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