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Identification of novel self lipids, GlcCer and GalCer, as CD1d-restricted ligands for type II NKT cells

Poster
Authors Sara Rhost
Jan-Eric Månsson
Susann Teneberg
Maria K. Blomqvist
Linda Löfbom
Susanna Cardell
Published in 6th International Symposium on CD1 and NKT Cells, September 23 - 27, 2011 - Chicago, Illinois. USA
Publication year 2011
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Keywords NKT cells, Glycolipids, CD1d
Subject categories Microbiology in the medical area

Abstract

NKT cells make up a potent immunomodulating subset of T lymphocytes that recognizes self-lipids presented by CD1d molecules. So far, the identity of most self-lipids presented by CD1d underlying the autoreactivity of NKT cells are unknown. In this study, we set out to identify self-lipids causing autoreactivity of a sulfatide reactive, CD1d restricted, murine type II NKT cell hybridoma (XV19). To this end we fractionated lipids from a highly stimulatory antigen presenting cell, A20CD1d TD, and found an active lipid fraction containing two isoforms of glucosylceramide (GlcCer) (Glcβ1-1'Cer), C24:0 and C16:0. The use of semi-synthetic isoforms confirmed that GlcCer stimulated XV19 NKT cells, In addition we identified the activation of XV19 cells by galactosylceramide (GalCer) isoforms (Galβ1-1'Cer), the precursors of sulfatide. The most potent isoform of the three glycosphingolipids was the lysoforms lacking the fatty acid chain followed by isoforms with the long fatty acid chain of C24. Thus, one NKT cell hybridoma could recognize sulfatide > GlcCer > GalCer in a CD1d-dependent manner. Ongoing studies are investigating the role of the identified ligands for the CD1d-dependent autoreacticity of the XV19 NKT hybridoma cells.

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