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Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis

SANDRINE ASPESLAGH UGent, Yali Li, Esther Dawen Yu, Nora Pauwels UGent, Matthias Trappeniers UGent, Enrico Girard, Tine Decruy UGent, Katrien Van Beneden UGent, Koen Venken UGent and Michael Drennan UGent, et al. (2011) EMBO JOURNAL. 30(11). p.2294-2305
abstract
Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic alpha-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Thl response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, alpha-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CD1d, glycolipids, iNKT cells, KILLER T-CELLS, LIGAND ALPHA-GALACTOSYLCERAMIDE, NKT CELLS, DENDRITIC CELLS, ACTIVATION, RECOGNITION, RECEPTOR, MICE, GAMMA, GLYCOLIPIDS
journal title
EMBO JOURNAL
Embo J.
volume
30
issue
11
pages
2294 - 2305
Web of Science type
Article
Web of Science id
000292424700019
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
9.205 (2011)
JCR rank
21/286 (2011)
JCR quartile
1 (2011)
ISSN
0261-4189
DOI
10.1038/emboj.2011.145
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1254280
handle
http://hdl.handle.net/1854/LU-1254280
date created
2011-06-06 16:01:35
date last changed
2013-02-27 09:09:11
@article{1254280,
  abstract     = {Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic alpha-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Thl response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, alpha-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo.},
  author       = {ASPESLAGH, SANDRINE and Li, Yali and Yu, Esther Dawen and Pauwels, Nora and Trappeniers, Matthias and Girard, Enrico and Decruy, Tine and Van Beneden, Katrien and Venken, Koen and Drennan, Michael and Leybaert, Luc and Wang, Jing and Franck, Richard W and Van Calenbergh, Serge and Zajonc, Dirk M and Elewaut, Dirk},
  issn         = {0261-4189},
  journal      = {EMBO JOURNAL},
  keyword      = {CD1d,glycolipids,iNKT cells,KILLER T-CELLS,LIGAND ALPHA-GALACTOSYLCERAMIDE,NKT CELLS,DENDRITIC CELLS,ACTIVATION,RECOGNITION,RECEPTOR,MICE,GAMMA,GLYCOLIPIDS},
  language     = {eng},
  number       = {11},
  pages        = {2294--2305},
  title        = {Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis},
  url          = {http://dx.doi.org/10.1038/emboj.2011.145},
  volume       = {30},
  year         = {2011},
}

Chicago
Aspeslagh, Sandrine, Yali Li, Esther Dawen Yu, Nora Pauwels, Matthias Trappeniers, Enrico Girard, Tine Decruy, et al. 2011. “Galactose-modified iNKT Cell Agonists Stabilized by an Induced Fit of CD1d Prevent Tumour Metastasis.” Embo Journal 30 (11): 2294–2305.
APA
Aspeslagh, S., Li, Y., Yu, E. D., Pauwels, N., Trappeniers, M., Girard, E., Decruy, T., et al. (2011). Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis. EMBO JOURNAL, 30(11), 2294–2305.
Vancouver
1.
Aspeslagh S, Li Y, Yu ED, Pauwels N, Trappeniers M, Girard E, et al. Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis. EMBO JOURNAL. 2011;30(11):2294–305.
MLA
Aspeslagh, Sandrine, Yali Li, Esther Dawen Yu, et al. “Galactose-modified iNKT Cell Agonists Stabilized by an Induced Fit of CD1d Prevent Tumour Metastasis.” EMBO JOURNAL 30.11 (2011): 2294–2305. Print.