Autoreactivity to Sulfatide by Human Invariant NKT Cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Annelein M StaxPeter van den Elzen

Abstract

Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup. Surface plasmon resonance shows that the affinity of human CD1d-sulfatide for the iNKT cell receptor is relatively low compared with CD1d-α-galactosylceramide (KD of 19-26 μM versus 1 μM). Apolipoprotein E isolated from human cerebrospinal fluid carries sulfatide that can be captured by APCs and presented by CD1d to iNKT cells. APCs from patients with metachromatic leukodystrophy, who accumulate sulfatides due to a deficiency in arylsulfatase-A, directly activate iNKT cells. Thus, we have identified sulfatide as a self-lipid recognized by human iNKT cells and propose that sulfatide recognition by innate T cells may be an important pathologic feature of neuroinflammatory dis...Continue Reading

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Citations

May 28, 2020·European Journal of Immunology·Jeanne PerroteauLaetitia Gautreau-Rolland
Jun 25, 2019·Frontiers in Cellular Neuroscience·Yu Cui, Qi Wan
Jun 13, 2018·Frontiers in Immunology·Francesca A VerversHenk S Schipper

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