Identification of novel glycolipid ligands activating a sulfatide-reactive, CD1d-restricted, type II natural killer T lymphocyte.
Sulfatide-reactive CD1d-restricted natural killer T (NKT) lymphocytes belong to the type II NKT cell subset with diverse TCRs, and have been found to regulate experimental auto-immune encephalomyelitis, tumor immunity, and experimental hepatitis in murine models. NKT cells can be activated by self-lipids presented by CD1d, manifested as autoreactivity. The identity of most of these self-lipids remains unknown. By isolating lipids from a CD1d-expressing, highly stimulatory antigen presenting cell, we identified isoforms of β-glucosylceramide (GlcCer), with sphingosine and fatty acid chain lengths of C24:0 and C16:0, that activated a sulfatide-reactive type II NKT cell hybridoma. A screen of structurally related glycosphingolipids demonstrated β-galactosylceramide (GalCer) as another ligand, and further, that the lysoforms were the most potent isoform of the glycosphingo-lipid ligands, followed by isoforms with a long fatty acid chain of C24. Thus, the same type II NKT cell was activated by several ligands, namely sulfatide, GlcCer, and GalCer. However, CD1d-dependent reactivity to antigen presenting cells lacking all GlcCer-based glycosphingolipids, or all glycosphingolipids, was maintained. This suggests that other endogenous, nonglycosphingolipid, lipid ligands contribute to steady-state autoreactivity by type II NKT cells.
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Sara
S
Rhost
Linda
L
Löfbom
Britt-Marie
BM
Rynmark
Bo
B
Pei
Jan-Eric
JE
Månsson
Susann
S
Teneberg
Maria
M
Blomqvist
Susanna L
SL
Cardell
D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D005963:Glucosylceramides / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D021241:Spectrometry, Mass, Electrospray Ionization; D013433:Sulfoglycosphingolipids / Q000276:immunology*; D053719:Tandem Mass Spectrometry
D055610:Antigens, CD1d; D005699:Galactosylceramides; D005963:Glucosylceramides; D013433:Sulfoglycosphingolipids