CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution.
Natural killer (NK) T cells are a lymphocyte subset with a distinct surface phenotype, an invariant T cell receptor (TCR), and reactivity to CD1. Here we show that mouse NK T cells can recognize human CD1d as well as mouse CD1, and human NK T cells also recognize both CD1 homologues. The unprecedented degree of conservation of this T cell recognition system suggests that it is fundamentally important. Mouse or human CD1 molecules can present the glycolipid alpha-galactosylceramide (alpha-GalCer) to NK T cells from either species. Human T cells, preselected for invariant Valpha24 TCR expression, uniformly recognize alpha-GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with alpha-GalCer led to the dramatic expansion of NK T cells with an invariant (Valpha24(+)) TCR and the release of large amounts of cytokines. Because invariant Valpha14(+) and Valpha24(+) NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that alpha-GalCer could be a useful agent for modulating human immune responses by activation of the highly conserved NK T cell subset.
La Jolla Institute of Allergy and Immunology, San Diego, California 92121, USA.
L
L
Brossay
M
M
Chioda
N
N
Burdin
Y
Y
Koezuka
G
G
Casorati
P
P
Dellabona
M
M
Kronenberg
D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000502:physiology*; D005075:Biological Evolution; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006825:Hybridomas; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis
D018949:Antigens, CD1; D002518:Ceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta