ACS Medicinal Chemistry Letters
Letter
Vα14 NKT Cells by Glycosylceramides. Science 1997, 278, 1626−
1629.
ASSOCIATED CONTENT
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S
* Supporting Information
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Detailed synthetic procedure, spectroscopic data, and full
characterizations of all new compounds, and procedures for
biological experiments including ELISA assay and in vivo study.
This material is available free of charge via the Internet at
AUTHOR INFORMATION
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Corresponding Author
Funding
This study was supported by (1) the National Research
Foundation of Korea (NRF); (2) the WCU program of the
NRF, funded by the Korean Ministry of Education, Science,
and Technology (MEST); and (3) MarineBio Program funded
by Ministry of Land, Transport, and Maritime Affairs (MLTM),
Korea. Y.K. and J.K. are grateful for the fellowships awarded by
the BK21 Program and the Seoul Science Fellowships.
(16) Trappeniers, M.; Beneden, K. V.; Decruy, T.; Hillaert, U.;
Linclau, B.; Elewaut, D.; Calenbergh, S. V. 6′-Derivatised α-GalCer
Analogues Capable of Inducing Strong CD1d-Mediated Th1-Biased
NKT Cell Responses in Mice. J. Am. Chem. Soc. 2008, 130, 16468−
16469.
(17) Chang, Y.-J.; Huang, J.-R.; Tsai, Y.-C.; Hung, J.-T.; Wu, D.;
Fujio, M.; Wong, C.-H.; Yu, A. L. Potent immune-modulating and
anticancer effects of NKT cell stimulatory glycolipids. Proc. Natl. Acad.
Sci. U.S.A. 2007, 104, 10299−10304.
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Wong, C.-H. Structure-Based Discovery of Glycolipids for CD1d-
Mediated NKT Cell Activation: Tuning the Adjuvant versus
Immunosuppression Activity. J. Am. Chem. Soc. 2006, 128, 9022−
9023.
(19) Goff, R. D.; Gao, Y.; Mattner, J.; Zhou, D.; Yin, N.; Cantu, C.;
Teyton, L.; Bendelac, A.; Savage, P. B. Effects of Lipid Chain Lengths
in α-Galactosylceramides on Cytokine Release by Natural Killer T
Cells. J. Am. Chem. Soc. 2004, 126, 13602−13603.
Notes
The authors declare no competing financial interest.
ABBREVIATIONS
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α-GalCer, α-galactosylceramide; iNKT cell, invariant natural
killer T cell; APC, antigen-presenting cell; TCR, T cell receptor;
IFN-γ, interferon-γ; IL-4, interleukin-4; ELISA, enzyme-linked
immunosorbent assay
(20) Yu, K. O. A.; Im, J. S.; Molano, A.; Dutronc, Y.; Illarionov, P. A.;
Forestier, C.; Fujiwara, N.; Arias, I.; Miyake, S.; Yamamura, T.; Chang,
Y.-T.; Besra, G. S.; Porcelli, S. A. Modulation of CD1d-restricted NKT
cell responses by using N-acyl variants of α-galactosylceramides. Proc.
Natl. Acad. Sci. U.S.A. 2005, 102, 3383−3388.
(21) McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.;
Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.;
Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.;
van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.;
Cerundolo, V. The length of lipids bound to human CD1d molecules
modulates the affinity of NKT cell TCR and the threshold of NKT cell
activation. J. Exp. Med. 2007, 204, 1131−1144.
(22) Zajonc, D. M.; Cantu, C.; Mattner, J.; Zhou, D.; Savage, P. B.;
Bendelac, A.; Wilson, I. A.; Teyton, L. Structure and function of a
potent agonist for the semi-invariant natural killer T cell receptor. Nat.
Immunol. 2005, 6, 810−818.
(23) Koch, M.; Stronge, V. S.; Shepherd, D.; Gadola, S. D.; Mathew,
B.; Ritter, G.; Fersht, A. R.; Besra, G. S.; Schmidt, R. R.; Jones, E. Y.;
Cerundolo, V. The crystal structure of human CD1d with and without
α-galactosylceramide. Nat. Immunol. 2005, 6, 819−826.
(24) Pellicci, D. G.; Patel, O.; Kjer-Nielsen, L.; Pang, S. S.; Sullivan,
L. C.; Kyparissoudis, K.; Brooks, A. G.; Reid, H. H.; Gras, S.; Lucet,
I. S.; Koh, R.; Smyth, M. J.; Mallevaey, T.; Matsuda, J. L.; Gapin, L.;
McCluskey, J.; Godfrey, D. I.; Rossjohn, J. Differential Recognition of
CD1d-α-Galactosyl Ceramide by the Vβ8.2 and Vβ7 Semi-invariant
NKT T Cell Receptors. Immunity 2009, 31, 47.
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