The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/10/1521/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 8, October 19, 1998 1521-1528

Articles

CD1d-mediated Recognition of an {alpha}-Galactosylceramide by Natural Killer T Cells Is Highly Conserved through Mammalian Evolution

Laurent Brossay*, Mariacristina Chioda{ddagger}, Nicolas Burdin*, Yasuhiko Koezuka§, Giulia Casorati{ddagger}, Paolo Dellabona{ddagger}, and Mitchell Kronenberg*

From the * La Jolla Institute of Allergy and Immunology, San Diego, California 92121; {ddagger} DIBIT, H.S. Raffaele Institute, I-20132 Milano, Italy; and § Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma 370-12, Japan

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 V{alpha}24 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 (V{alpha}24+) TCR and the release of large amounts of cytokines. Because invariant V{alpha}14+ and V{alpha}24+ 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.

Key Words: CD1 • natural killer T cells • antigen presentation • glycolipid • cytokines

Address correspondence to Mitchell Kronenberg, La Jolla Institute of Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: 619-678-4540; Fax: 619-678-4595; E-mail: mitch{at}liai.org

Abbreviations used: {alpha}-GalCer, {alpha}-galactosylceramide; β2m, β2-microglobulin; hCD1d, human CD1d; mCD1, mouse CD1.


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