CD 1 d - mediated Recognition of an a - 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 a -galactosylceramide ( a -GalCer) to NK T cells from either species. Human T cells, preselected for invariant V a 24 TCR expression, uniformly recognize a -GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with a -GalCer led to the dramatic expansion of NK T cells with an invariant (V a 24 1 ) TCR and the release of large amounts of cytokines. Because invariant V a 14 1 and V a 24 1 NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that a -GalCer could be a useful agent for modulating human immune responses by activation of the highly conserved NK T cell subset.