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.
Zhou
Dapeng
D
University of Chicago, Department of Pathology, Chicago, IL 60637, USA. dzhou@midway.uchicago.edu
Mattner
Jochen
J
Cantu
Carlos
C
Schrantz
Nicolas
N
Yin
Ning
N
Gao
Ying
Y
Sagiv
Yuval
Y
Hudspeth
Kelly
K
Wu
Yun-Ping
YP
Yamashita
Tadashi
T
Teneberg
Susann
S
Wang
Dacheng
D
Proia
Richard L
RL
Levery
Steven B
SB
Savage
Paul B
PB
Teyton
Luc
L
Bendelac
Albert
A
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
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