Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

TY - JOUR

T1 - Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

AU - Blomqvist, Maria

AU - Rhost, Sara

AU - Teneberg, Susann

AU - Löfbom, Linda

AU - Østerbye, Thomas

AU - Brigl, Manfred

AU - Månsson, Jan-Eric

AU - Cardell, Susanna L

PY - 2009/7/1

Y1 - 2009/7/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antigen-Presenting Cells

KW - Antigens, CD1d

KW - Cells, Cultured

KW - Dendritic Cells

KW - Enzyme-Linked Immunosorbent Assay

KW - Fatty Acids

KW - Flow Cytometry

KW - Hybridomas

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Inbred Strains

KW - Mice, Knockout

KW - Natural Killer T-Cells

KW - Spleen

KW - Sulfoglycosphingolipids

U2 - 10.1002/eji.200839001

DO - 10.1002/eji.200839001

M3 - Journal article

C2 - 19582739

SN - 1426-3912

VL - 39

SP - 1726

EP - 1735

JO - Central-European Journal of Immunology

JF - Central-European Journal of Immunology

IS - 7

ER -