CD1d-mediated recognition of an α-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution

L Brossay, M Chioda, N Burdin, Y Koezuka… - The Journal of …, 1998 - rupress.org
L Brossay, M Chioda, N Burdin, Y Koezuka, G Casorati, P Dellabona, M Kronenberg
The Journal of experimental medicine, 1998rupress.org
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 α-galactosylceramide (α-GalCer) to NK T cells from either species …
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 α-galactosylceramide (α-GalCer) to NK T cells from either species. Human T cells, preselected for invariant Vα24 TCR expression, uniformly recognize α-GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with α-GalCer led to the dramatic expansion of NK T cells with an invariant (Vα24+) TCR and the release of large amounts of cytokines. Because invariant Vα14+ and Vα24+ NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that α-GalCer could be a useful agent for modulating human immune responses by activation of the highly conserved NK T cell subset.
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