Selective ability of mouse CD1 to present glycolipids: alpha-galactosylceramide specifically stimulates V alpha 14+ NK T lymphocytes.
Mouse CD1 (mCD1) glycoproteins are known to present peptides, while human CD1 molecules present glycolipids. In mice, mCD1-autoreactive NK T cells play critical roles in various immune responses, through the secretion of high amounts of cytokines. This study was initiated to determine whether glycolipids are involved in the autorecognition of mCD1 by NK T cells. Alpha-galactosylceramide (alpha-GalCer) was the only glycolipid tested capable of eliciting an mCD1-restricted response by splenic T cells. Moreover, splenic T cells derived from mCD1-deficient mice were not stimulated by alpha-GalCer, suggesting that the responsive T cells are selected by mCD1. Using cytoflow techniques, we confirmed that, in response to alpha-GalCer, IFN-gamma-secreting cells displayed an NK T cell phenotype. The predominance of IFN-gamma vs IL-4, however, is determined by the type of mCD1+ APC, suggesting the potential for APC regulation of cytokine production by NK T cells. Among a panel of 10 mCD1-autoreactive T cell hybridomas, only the ones that express the typical V alpha 14 J alpha 281 TCR rearrangement of NK T cells responded to alpha-GalCer. Fixation or treatment of mCD1+ APCs with an inhibitor of endosomal acidification and the use of mCD1 mutants unable to traffic through endosome still allowed alpha-GalCer to stimulate NK T cells. Thus, endosomal trafficking and Ag processing are not required for glycolipid recognition. In summary, alpha-GalCer might be the autologous ligand, or a mimic of a glycolipid ligand, involved in the mCD1-mediated stimulation of NK T cells.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
N
N
Burdin
L
L
Brossay
Y
Y
Koezuka
S T
ST
Smiley
M J
MJ
Grusby
M
M
Gui
M
M
Taniguchi
K
K
Hayakawa
M
M
Kronenberg
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology; D006017:Glycolipids / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D018949:Antigens, CD1; D005699:Galactosylceramides; D006017:Glycolipids; D011948:Receptors, Antigen, T-Cell