PMID- 23658796
OWN - NLM
STAT- MEDLINE
DCOM- 20131204
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Direct activation of human dendritic cells by particle-bound but not soluble MHC 
      class II ligand.
PG  - e63039
LID - 10.1371/journal.pone.0063039 [doi]
LID - e63039
AB  - Dendritic cells (DCs) are key activators of cellular immune responses through 
      their capacity to induce naive T cells and sustained effector T cell responses. 
      This capacity is a function of their superior efficiency of antigen presentation 
      via MHC class I and class II molecules, and the expression of co-stimulatory cell 
      surface molecules and cytokines. Maturation of DCs is induced by microbial 
      factors via pattern recognition receptors such as Toll-like receptors, 
      pro-inflammatory cytokines or cognate interaction with CD4(+) T cells. Here we 
      show that, unexpectedly, the PanDR helper T cell epitope PADRE, a generic T 
      helper cell antigen presented by a large fraction of HLA-DR alleles, when 
      delivered in particle-bound form induced maturation of human DCs. The DCs that 
      received the particle-bound PADRE displayed all features of fully mature DCs, 
      such as high expression of the co-stimulatory molecules CD80, CD86, CD83, the 
      MHC-II molecule HLA-DR, secretion of high levels of the biologically active IL-12 
      (IL-12p70) and induction of vigorous proliferation of naive CD4(+) T cells. 
      Furthermore, the maturation of DCs induced by particle-bound PADRE was shown to 
      involve sphingosine kinase, calcium signaling from internal sources and 
      downstream signaling through the MAP kinase and the p72syk pathways, and finally 
      activation of the transcription factor NF-kappaB. Based on our findings, we propose 
      that particle-bound PADRE may be used as a DC activator in DC-based vaccines.
FAU - Baleeiro, Renato B
AU  - Baleeiro RB
AD  - Charite-Universitatsmedizin Berlin, Department of Dermatology, Venerology and 
      Allergology, Berlin, Germany.
FAU - Wiesmuller, Karl-Heinz
AU  - Wiesmuller KH
FAU - Dahne, Lars
AU  - Dahne L
FAU - Lademann, Jurgen
AU  - Lademann J
FAU - Barbuto, Jose A
AU  - Barbuto JA
FAU - Walden, Peter
AU  - Walden P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130502
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Calmodulin)
RN  - 0 (Malaria Vaccines)
RN  - 0 (PADRE 45)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Calcium Signaling/drug effects
MH  - Calmodulin/metabolism
MH  - Cell Differentiation/drug effects
MH  - Dendritic Cells/cytology/*drug effects/immunology
MH  - Humans
MH  - Intracellular Space/drug effects/metabolism
MH  - Malaria Vaccines/*chemistry/*pharmacology
MH  - Phenotype
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Solubility
MH  - T-Lymphocytes/cytology/drug effects/immunology
PMC - PMC3642081
COIS- Competing Interests: RBB, JL, JAMB and PW have declared that no competing 
      interests exist. KHW is CEO of the company EMC microcollection GmbH in Tubingen 
      and LD of the company Surflay Nanotec GmbH in Berlin, Germany. This does not 
      alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials.
EDAT- 2013/05/10 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/05/02
CRDT- 2013/05/10 06:00
PHST- 2013/02/13 00:00 [received]
PHST- 2013/03/28 00:00 [accepted]
PHST- 2013/05/10 06:00 [entrez]
PHST- 2013/05/10 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/05/02 00:00 [pmc-release]
AID - PONE-D-13-06505 [pii]
AID - 10.1371/journal.pone.0063039 [doi]
PST - epublish
SO  - PLoS One. 2013 May 2;8(5):e63039. doi: 10.1371/journal.pone.0063039. Print 2013.