Glycolipids that elicit IFN-γ-biased responses from natural killer T cells.
Chem Biol
; 18(12): 1620-30, 2011 Dec 23.
Article
in En
| MEDLINE
| ID: mdl-22195564
ABSTRACT
Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, α-galactosyl ceramide (αGalCer), is a potential anticancer agent whose activity depends upon IFN-γ secretion. We report two analogs of αGalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-γ that correlates with detergent-resistant binding to CD1d and an increased stability of the lipid-CD1d complexes on antigen-presenting cells. Structural analysis on one of the analogs indicates that it is more deeply bound inside the CD1d groove, suggesting tighter lipid-CD1d interactions. To our knowledge, this is the first example in which structural information provides an explanation for the increased lipid-CD1d stability, likely responsible for the Th1 bias. We provide insights into the mechanism of IFN-γ-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycolipids
/
Interferon-gamma
/
Natural Killer T-Cells
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Chem Biol
Journal subject:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Year:
2011
Type:
Article
Affiliation country:
United States