title: Lysosomal glycosphingolipid recognition by NKT cells.
abstract: 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.
authors.affiliation: University of Chicago, Department of Pathology, Chicago, IL 60637, USA. dzhou@midway.uchicago.edu
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhou
authors.forename: Jochen
authors.initials: J
authors.lastname: Mattner
authors.forename: Carlos
authors.initials: C
authors.lastname: Cantu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schrantz
authors.forename: Ning
authors.initials: N
authors.lastname: Yin
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Yuval
authors.initials: Y
authors.lastname: Sagiv
authors.forename: Kelly
authors.initials: K
authors.lastname: Hudspeth
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Wu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Susann
authors.initials: S
authors.lastname: Teneberg
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Steven B
authors.initials: SB
authors.lastname: Levery
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d; D015551:Autoimmunity; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D005915:Globosides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007239:Infections / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology; D037121:Plant Lectins / Q000276:immunology; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D049231:Saposins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005915:Globosides; C045475:Griffonia simplicifolia lectins; D008024:Ligands; D037121:Plant Lectins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D049231:Saposins; C037097:isoglobotriaosylceramide; D005700:Galactosyltransferases; C413211:UDP-galactose beta-D-galactosyl-1,4-glycosylceramide alpha-1,3-galactosyltransferase; D001619:beta-N-Acetylhexosaminidases