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Recognition of lysophosphatidylcholine by type II NKT cells and protection from
an inflammatory liver disease
#MMPMID25261475
Maricic I
; Girardi E
; Zajonc DM
; Kumar V
J Immunol
2014[Nov]; 193
(9
): 4580-9
PMID25261475
show ga
Lipids presented by the MHC class I-like molecule, CD1d, are recognized by NK T
(NKT) cells, which can be broadly categorized into two subsets. The
well-characterized type I NKT cells express a semi-invariant TCR and can
recognize both ?- and ?-linked glycolipids, whereas type II NKT cells are less
well studied, express a relatively diverse TCR repertoire, and recognize ?-linked
lipids. Recent structural studies have shown a distinct mode of recognition of a
self-glycolipid sulfatide bound to CD1d by a type II NKT TCR. To further
characterize Ag recognition by these cells, we have used the structural data and
screened other small molecules able to bind to CD1d and activate type II NKT
cells. Using plate-bound CD1d and APC-based Ag presentation assay, we found that
phospholipids such as lysophosphatidylcholine (LPC) can stimulate the
sulfatide-reactive type II NKT hybridoma Hy19.3 in a CD1d-dependent manner. Using
plasmon resonance studies, we found that this type II NKT TCR binds with
CD1d-bound LPC with micromolar affinities similar to that for sulfatide.
Furthermore, LPC-mediated activation of type II NKT cells leads to anergy
induction in type I NKT cells and affords protection from Con A-induced
hepatitis. These data indicate that, in addition to self-glycolipids,
self-lysophospholipids are also recognized by type II NKT cells. Because
lysophospholipids are involved during inflammation, our findings have
implications for not only understanding activation of type II NKT cells in
physiological settings, but also for the development of immune intervention in
inflammatory diseases.
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