IFN-gamma enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation.
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.
Matsuo
Mitsutoshi
M
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Nagata
Yasuhiro
Y
Sato
Eiichi
E
Atanackovic
Djordje
D
Valmori
Danila
D
Chen
Yao-Tseng
YT
Ritter
Gerd
G
Mellman
Ira
I
Old
Lloyd J
LJ
Gnjatic
Sacha
S
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D010641:Phenotype; D011994:Recombinant Proteins; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma