V alpha 14 NKT Cells - A novel lymphocyte specific for glycolipid antigens |
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V alpha 14 NKT cells are a novel line of lymphocytes characterized
by co-expression of an invariant antigen receptor (V alpha 14)
and an NK marker, NK1.1. V alpha 14 NKT cells are a major source
of interleukin-4 and interferon-gamma in vivo, exert cytotoxicity
against tumor cells, and play a role in the onset of autoimmune
diseases. V alpha 14 NKT cells recognize a non-classical MHC
class I molecule CD1d; and mice deficient for the CD1d have a
drastically reduced number of V alpha 14 NKT cells. The ligand
for the V alpha 14 antigen receptor, however, remained elusive
until recently. In 1997, we identified for the first time one
such ligand through experiments using V alpha 14 NKT cell-deficient
mice and V alpha 14 NKT mice generated by gene targeting and
transgenic technologies (1). The ligand for V alpha 14 receptor
turned out to be a glycosphingolipid, alpha-galactosylceramide
(alpha-GalCer). The alpha-galactosylceramide activates V alpha
14 NKT cells to be cytotoxic against tumor cells in vitro, and
causes experimental metastatic tumor rejection when injected
in vivo (2). Although glycosylceramides are a major component of the mammalian body, only beta-anomers have been known. The alpha-galactosylceramide, therefore, may represent an exogenous antigen. By contrast, glycophosphatidylinositol (GPI) has recently been reported to be a natural ligand for CD1d (3). The immune system can recognize peptide and oligosaccharide antigens via conventional T cells and NK cells, respectively. The current study has shed light to a novel mode of antigen recognition by immune cells, i.e. the recognition of glycolipids by V alpha 14 NKT cells. |
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| Tetsu Kawano and Masaru Taniguchi (Department of Molecular Immunology, Graduate School of Medicine, Chiba University ) | ||||||||||||||
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| Jun.15, 1998 | ||||||||||||||
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