Abstract
We compared monocyte-derived dendritic cells and transforming growth factor-beta1-induced Langerhans-like cells (LCs) for their capacity to cross-present exogenous NY-ESO-1 protein/antibody immune complexes to an NY-ESO-1-specific CD8+ T cell clone. In contrast to dendritic cells, LCs were not able to cross-present NY-ESO-1 to the T cell clone constitutively but did so after treatment with IFN-gamma. Remarkably, this IFN-gamma-inducible characteristic was due neither to enhanced antigen uptake nor to facilitated antigen processing in LCs. Rather, IFN-gamma acted at least in part by potentiating the maturation of otherwise refractory LCs, enabling in turn exogenous antigen to reach the processing machinery. This model of conditional cross-presentation establishes an original level of action for IFN-gamma as an effective immune modulator and supports the use of IFN-gamma in protein vaccination strategies targeting LCs.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antigen Presentation / drug effects
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Cell Differentiation / drug effects
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Cell Line
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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HLA-A Antigens / metabolism
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HLA-A2 Antigen
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Humans
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Interferon-gamma / pharmacology*
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Langerhans Cells / cytology
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Langerhans Cells / drug effects*
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Langerhans Cells / immunology*
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Molecular Sequence Data
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Phenotype
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Recombinant Proteins
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Signal Transduction
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta1
Substances
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Antigens, Neoplasm
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CTAG1B protein, human
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HLA-A Antigens
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HLA-A*02:01 antigen
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HLA-A2 Antigen
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Membrane Proteins
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Recombinant Proteins
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TGFB1 protein, human
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Interferon-gamma