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Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells
Maria Blomqvist1, Sara Rhost, Susann Teneberg
1Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Sweden.
European Journal of Immunology
|July 8, 2009
Summary
Sulfatide, a lipid found in myelin and pancreatic cells, is recognized by CD1d-restricted NKT cells. Different sulfatide structures vary in their ability to activate these immune cells.
Area of Science:
- Immunology
- Neuroscience
- Glycobiology
Background:
- Sulfatide (SO(3)-3Galbeta1Cer) is a glycosphingolipid that acts as a ligand for CD1d-restricted NKT cells.
- These NKT cells play roles in autoimmune diseases like multiple sclerosis, tumor immunity, and hepatitis.
- Native sulfatides exist as a mixture of isoforms with varying lipid chain compositions.
Purpose of the Study:
- To investigate the recognition of different sulfatide isoforms by sulfatide-specific CD1d-restricted NKT hybridomas.
- To determine which sulfatide structures are most potent in stimulating NKT cells.
- To clarify the role of sulfatide in natural autoreactivity.
Main Methods:
- Utilized sulfatide-specific CD1d-restricted murine NKT hybridomas.
- Tested the recognition of various sulfatide isoforms, including those with different fatty acid chain lengths and saturation.
- Assessed the stimulatory capacity of different sulfatide structures.
Main Results:
- Sulfatide-specific NKT hybridomas recognized multiple sulfatide isoforms, including C24:1, C24:0, and C16:0.
- Lysosulfatide (lacking a fatty acid) was the most potent stimulatory isoform.
- Shortened fatty acid chains, saturation, and hydroxylation of the fatty acid reduced or abolished NKT cell stimulatory capacity.
- Sulfatide was not responsible for the autoreactivity observed in XV19 T hybridoma cells.
Conclusions:
- CD1d-restricted NKT cells exhibit promiscuity in recognizing various sulfatide isoforms.
- Sulfatide, a key component of myelin and pancreatic beta-cells, is identified as a natural ligand for type II CD1d-restricted NKT cells.
- Understanding sulfatide recognition by NKT cells may offer insights into autoimmune diseases and cancer immunity.
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