Lysosomal glycosphingolipid recognition by NKT cells.

• NKT cells represent a distinct lineage of T cells that coexpress a conserved alphabeta T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking beta-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity.

Keyword

Animals

Antigen Presentation

Antigens

CD1

immunology

metabolism

Autoimmunity

Cell Line

Cell Line

Tumor

Cells

Cultured

Dendritic Cells

immunology

Galactosyltransferases

genetics

metabolism

Globosides

chemistry

immunology

metabolism

Humans

Hybridomas

Infection

immunology

Killer Cells

Natural

immunology

Ligands

Lymphocyte Activation

Lymphocyte Count

Lysosomes

metabolism

Mice

Mice

Inbred C57BL

Neoplasms

immunology

Plant Lectins

immunology

Rats

Receptors

Antigen

T-Cell

alpha-beta

immunology

Saposins

metabolism

T-Lymphocyte Subsets

immunology

beta-N-Acetylhexosaminidase

genetics

metabolism

Publication and Content Type

ref (subject category)

art (subject category)