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Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen-presenting potential of plasmacytoid DCs

Mirjam Kool UGent, Corine GeurtsVanKessel, Femke Muskens, Filipe Branco Madeira UGent, Menno van Nimwegen, Harmjan Kuipers, Kris Thielemans, Henk C Hoogsteden, Hamida Hammad UGent and Bart Lambrecht UGent (2011) JOURNAL OF LEUKOCYTE BIOLOGY. 90(6). p.1177-1190
abstract
Subsets of antigen-presenting cDCs have a differential capacity to present exogenous and endogenous protein antigens to CD4(+) and/or CD8(+) T lymphocytes, depending on expression of antigen-uptake receptors, processing machinery, and microbial instruction. pDCs are also capable of antigen presentation, but the conditions under which they do this have not been systematically addressed. Highly purified cDCs and pDCs were exposed to exogenous, soluble OVA peptide or whole protein. Alternatively, they were made to express cytoplasmic or endosomal OVA by retroviral transduction or by infection with influenza virus containing OVA epitopes. Like cDCs, pDCs expressed the MHC I processing machinery and could present endogenous or cross-present exogenous OVA to CD8(+) T cells, provided they had been stimulated by CpG motif TLR9 ligands or by influenza. Unlike cDCs, the cross-priming activity of pDCs was enhanced, not decreased, by simultaneous TLR stimulation. Processing and presentation of exogenous OVA to CD4(+) T cells required TLR9 ligation prior to antigen encounter and addition of OVA-specific Igs. These stimuli up-regulated critical MHC II processing machinery and enhanced routing to acidic endosomal organelles in a Fc gamma RII-dependent manner. Endogenous antigen was not presented to CD4(+) T cells when expressed in the cytoplasm of pDCs by retrovirus or contained in influenza, unless an Ii-chain-derived endosomal routing signal was present. Thus, timing of TLR ligation and facilitated antigen uptake dictate the potential of pDCs to present endogenous or exogenous antigen by influencing endosomal traffic and antigen-processing machinery.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
EXOGENOUS ANTIGENS, INTERFERON-ALPHA/BETA, DENDRITIC CELL SUBSETS, OVA, influenza, antigen processing, dentritic cells, ADAPTIVE IMMUNITY, CYTOPLASMIC DOMAIN HETEROGENEITY, BONE-MARROW CULTURES, CD8(+) T-CELLS, IN-VIVO, CROSS-PRESENTATION, INFLUENZA-VIRUS
journal title
JOURNAL OF LEUKOCYTE BIOLOGY
J. Leukoc. Biol.
volume
90
issue
6
pages
1177 - 1190
Web of Science type
Article
Web of Science id
000298154400016
JCR category
HEMATOLOGY
JCR impact factor
4.992 (2011)
JCR rank
12/68 (2011)
JCR quartile
1 (2011)
ISSN
0741-5400
DOI
10.1189/jlb.0610342
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2002825
handle
http://hdl.handle.net/1854/LU-2002825
date created
2012-01-25 12:03:15
date last changed
2016-12-19 15:39:19
@article{2002825,
  abstract     = {Subsets of antigen-presenting cDCs have a differential capacity to present exogenous and endogenous protein antigens to CD4(+) and/or CD8(+) T lymphocytes, depending on expression of antigen-uptake receptors, processing machinery, and microbial instruction. pDCs are also capable of antigen presentation, but the conditions under which they do this have not been systematically addressed. Highly purified cDCs and pDCs were exposed to exogenous, soluble OVA peptide or whole protein. Alternatively, they were made to express cytoplasmic or endosomal OVA by retroviral transduction or by infection with influenza virus containing OVA epitopes. Like cDCs, pDCs expressed the MHC I processing machinery and could present endogenous or cross-present exogenous OVA to CD8(+) T cells, provided they had been stimulated by CpG motif TLR9 ligands or by influenza. Unlike cDCs, the cross-priming activity of pDCs was enhanced, not decreased, by simultaneous TLR stimulation. Processing and presentation of exogenous OVA to CD4(+) T cells required TLR9 ligation prior to antigen encounter and addition of OVA-specific Igs. These stimuli up-regulated critical MHC II processing machinery and enhanced routing to acidic endosomal organelles in a Fc gamma RII-dependent manner. Endogenous antigen was not presented to CD4(+) T cells when expressed in the cytoplasm of pDCs by retrovirus or contained in influenza, unless an Ii-chain-derived endosomal routing signal was present. Thus, timing of TLR ligation and facilitated antigen uptake dictate the potential of pDCs to present endogenous or exogenous antigen by influencing endosomal traffic and antigen-processing machinery.},
  author       = {Kool, Mirjam and GeurtsVanKessel, Corine and Muskens, Femke and Branco Madeira, Filipe and van Nimwegen, Menno and Kuipers, Harmjan and Thielemans, Kris and Hoogsteden, Henk C and Hammad, Hamida and Lambrecht, Bart},
  issn         = {0741-5400},
  journal      = {JOURNAL OF LEUKOCYTE BIOLOGY},
  keyword      = {EXOGENOUS ANTIGENS,INTERFERON-ALPHA/BETA,DENDRITIC CELL SUBSETS,OVA,influenza,antigen processing,dentritic cells,ADAPTIVE IMMUNITY,CYTOPLASMIC DOMAIN HETEROGENEITY,BONE-MARROW CULTURES,CD8(+) T-CELLS,IN-VIVO,CROSS-PRESENTATION,INFLUENZA-VIRUS},
  language     = {eng},
  number       = {6},
  pages        = {1177--1190},
  title        = {Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen-presenting potential of plasmacytoid DCs},
  url          = {http://dx.doi.org/10.1189/jlb.0610342},
  volume       = {90},
  year         = {2011},
}

Chicago
Kool, Mirjam, Corine GeurtsVanKessel, Femke Muskens, Filipe Branco Madeira, Menno van Nimwegen, Harmjan Kuipers, Kris Thielemans, Henk C Hoogsteden, Hamida Hammad, and Bart Lambrecht. 2011. “Facilitated Antigen Uptake and Timed Exposure to TLR Ligands Dictate the Antigen-presenting Potential of Plasmacytoid DCs.” Journal of Leukocyte Biology 90 (6): 1177–1190.
APA
Kool, Mirjam, GeurtsVanKessel, C., Muskens, F., Branco Madeira, F., van Nimwegen, M., Kuipers, H., Thielemans, K., et al. (2011). Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen-presenting potential of plasmacytoid DCs. JOURNAL OF LEUKOCYTE BIOLOGY, 90(6), 1177–1190.
Vancouver
1.
Kool M, GeurtsVanKessel C, Muskens F, Branco Madeira F, van Nimwegen M, Kuipers H, et al. Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen-presenting potential of plasmacytoid DCs. JOURNAL OF LEUKOCYTE BIOLOGY. 2011;90(6):1177–90.
MLA
Kool, Mirjam, Corine GeurtsVanKessel, Femke Muskens, et al. “Facilitated Antigen Uptake and Timed Exposure to TLR Ligands Dictate the Antigen-presenting Potential of Plasmacytoid DCs.” JOURNAL OF LEUKOCYTE BIOLOGY 90.6 (2011): 1177–1190. Print.