Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 7, Pages 1726-1735Publisher
WILEY
DOI: 10.1002/eji.200839001
Keywords
Antigen presentation/processing; Autoimmunity; CD1 molecules; NKT cells Self/non-self discrimination
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Funding
- Swedish Cancer Foundation
- Swedish Research Council
- LUA-ALF Goteborg
- Novo Nordisk Foundation
- Swedish Diabetes Society
- Swedish Brain Foundation (HJarnfonden)
- Adlebert and W and M Lundgren
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The glycosphingolipid sulfatide (SO3-3Gal beta 1Cer) is a demonstrated ligand for a subset of CD1d-restricted NKT cells, which could regulate experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as tumor immunity and experimental hepatitis. Native sulfatide is a mixture of sulfatide isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Here, we demonstrate that sulfatide-specific CD1d-restricted murine NKT hybridomas recognized several different sulfatide isoforms. These included the physiologically relevant isoforms C24:1 and C24:0, major constituents of the myelin sheet of the nervous system, and C16:0, prominent in the pancreatic islet beta-cells. The most potent sulfatide isoform was lysosulfatide (lacking a fatty acid). Shortened fatty acid chain length (C24:1 versus C18:1), or saturation of the long fatty acid (C24:0), resulted in reduced stimulatory capacity, and fatty acid hydroxylation. abolished the response. Moreover, sulfatide was not responsible for the natural autoreactivity toward splenocytes by XV19 T hybridoma cells. Our results reveal a promiscuity in the recognition of sulfatide isoforms by a CD1d-restricted NKT-cell clone, and suggest that sulfatide, a major component of the myelin sheet and pancreatic beta-cells, is one of several natural ligands for type II CD1d-restricted NKT cells.
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