Abstract
The glycosphingolipid sulfatide (SO(3)-3Galbeta1Cer) 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.
| Original language | English |
|---|---|
| Journal | Central-European Journal of Immunology |
| Volume | 39 |
| Issue number | 7 |
| Pages (from-to) | 1726-35 |
| Number of pages | 10 |
| ISSN | 1426-3912 |
| DOIs | |
| Publication status | Published - 1 Jul 2009 |
Keywords
- Animals
- Antigen-Presenting Cells
- Antigens, CD1d
- Cells, Cultured
- Dendritic Cells
- Enzyme-Linked Immunosorbent Assay
- Fatty Acids
- Flow Cytometry
- Hybridomas
- Mice
- Mice, Inbred C57BL
- Mice, Inbred Strains
- Mice, Knockout
- Natural Killer T-Cells
- Spleen
- Sulfoglycosphingolipids
