Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides.
A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Valpha14i NKT cell agonists may prove to be useful in immunotherapeutic applications.
Yu
Karl O A
KO
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Im
Jin S
JS
Molano
Alberto
A
Dutronc
Yves
Y
Illarionov
Petr A
PA
Forestier
Claire
C
Fujiwara
Nagatoshi
N
Arias
Isa
I
Miyake
Sachiko
S
Yamamura
Takashi
T
Chang
Young-Tae
YT
Besra
Gurdyal S
GS
Porcelli
Steven A
SA
D000818:Animals; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D005699:Galactosylceramides; C103873:KRN 7000
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