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10.4049/jimmunol.1400699

http://scihub22266oqcxt.onion/10.4049/jimmunol.1400699
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C4201983!4201983!25261475
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suck abstract from ncbi


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pmid25261475      J+Immunol 2014 ; 193 (9): 4580-9
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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 PMID25261475show ga
  • Lipids presented by the major histocompatibility complex (MHC) class I-like molecule, CD1d, are recognized by natural killer T (NKT) cells, which can be broadly categorized into two subsets. The well-characterized type I NKT cells, express a semi-invariant T cell receptor (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 antigen 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 antigen 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 ConA-induced hepatitis. These data indicate that, in addition to self-glycolipids, self-lysophospholipids are also recognized by type II NKT cells. Since 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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