Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells.
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.
Blomqvist
Maria
M
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Sweden.
Rhost
Sara
S
Teneberg
Susann
S
Löfbom
Linda
L
Osterbye
Thomas
T
Brigl
Manfred
M
Månsson
Jan-Eric
JE
Cardell
Susanna L
SL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000737:chemistry / Q000276:immunology; D005434:Flow Cytometry; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D005227:Fatty Acids; D013433:Sulfoglycosphingolipids