J. Exp. Med., Volume 188, Number 8, October 19, 1998 1521-1528

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

By Laurent Brossay,^* Mariacristina Chioda, Nicolas Burdin,^* Yasuhiko Koezuka,^§ Giulia Casorati, Paolo Dellabona, and Mitchell Kronenberg^*

From the ^* La Jolla Institute of Allergy and Immunology, San Diego, California 92121;  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 -galactosylceramide (-GalCer) to NK T cells from either species. Human T cells, preselected for invariant V24 TCR expression, uniformly recognize -GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with -GalCer led to the dramatic expansion of NK T cells with an invariant (V24⁺) TCR and the release of large amounts of cytokines. Because invariant V14⁺ and V24⁺ NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that -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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• Hayes, S. M., Knight, K. L. (2001). Group 1 CD1 Genes in Rabbit. J. Immunol. 166: 403-410 [Abstract] [Full Text]  
• Pal, E., Tabira, T., Kawano, T., Taniguchi, M., Miyake, S., Yamamura, T. (2001). Costimulation-Dependent Modulation of Experimental Autoimmune Encephalomyelitis by Ligand Stimulation of V{{alpha}}14 NK T Cells. J. Immunol. 166: 662-668 [Abstract] [Full Text]  
• Laouini, D., Casrouge, A., Dalle, S., Lemonnier, F., Kourilsky, P., Kanellopoulos, J. (2000). V{beta} T Cell Repertoire of CD8+ Splenocytes Selected on Nonpolymorphic MHC Class I Molecules. J. Immunol. 165: 6381-6386 [Abstract] [Full Text]  
• Araujo, L. M., Puel, A., Gouarin, C., Hameg, A., Mevel, J.-C., Koezuka, Y., Bach, J.-F., Mouton, D., Herbelin, A. (2000). NKT lymphocyte ontogeny and function are impaired in low antibody-producer Biozzi mice: gene mapping in the interval-specific congenic strains raised for immunomodulatory genes. Int Immunol 12: 1613-1622 [Abstract] [Full Text]  
• Bonish, B., Jullien, D., Dutronc, Y., Huang, B. B., Modlin, R., Spada, F. M., Porcelli, S. A., Nickoloff, B. J. (2000). Overexpression of CD1d by Keratinocytes in Psoriasis and CD1d-Dependent IFN-{gamma} Production by NK-T Cells. J. Immunol. 165: 4076-4085 [Abstract] [Full Text]  
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• Apostolou, I., Cumano, A., Gachelin, G., Kourilsky, P. (2000). Evidence for Two Subgroups of CD4-CD8- NKT Cells with Distinct TCR{alpha}{beta} Repertoires and Differential Distribution in Lymphoid Tissues. J. Immunol. 165: 2481-2490 [Abstract] [Full Text]  
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• Fuji, N., Ueda, Y., Fujiwara, H., Itoh, T., Yoshimura, T., Yamagishi, H. (2000). Antitumor Effect of {{alpha}}-Galactosylceramide (KRN7000) on Spontaneous Hepatic Metastases Requires Endogenous Interleukin 12 in the Liver. Clin. Cancer Res. 6: 3380-3387 [Abstract] [Full Text]  
• Ishihara, S., Nieda, M., Kitayama, J., Osada, T., Yabe, T., Kikuchi, A., Koezuka, Y., Porcelli, S. A., Tadokoro, K., Nagawa, H., Juji, T. (2000). {alpha}-Glycosylceramides Enhance the Antitumor Cytotoxicity of Hepatic Lymphocytes Obtained from Cancer Patients by Activating CD3-CD56+ NK Cells In Vitro. J. Immunol. 165: 1659-1664 [Abstract] [Full Text]  
• Skold, M., Faizunnessa, N. N., Wang, C.-R., Cardell, S. (2000). CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR. J. Immunol. 165: 168-174 [Abstract] [Full Text]  
• Takahashi, T., Nieda, M., Koezuka, Y., Nicol, A., Porcelli, S. A., Ishikawa, Y., Tadokoro, K., Hirai, H., Juji, T. (2000). Analysis of Human V{alpha}24+ CD4+ NKT Cells Activated by {alpha}-Glycosylceramide-Pulsed Monocyte-Derived Dendritic Cells. J. Immunol. 164: 4458-4464 [Abstract] [Full Text]  
• Illes, Z., Kondo, T., Newcombe, J., Oka, N., Tabira, T., Yamamura, T. (2000). Differential Expression of NK T Cell V{alpha}24J{alpha}Q Invariant TCR Chain in the Lesions of Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy. J. Immunol. 164: 4375-4381 [Abstract] [Full Text]  
• van der Vliet, H. J. J., Nishi, N., de Gruijl, T. D., von Blomberg, B. M. E., van den Eertwegh, A. J. M., Pinedo, H. M., Giaccone, G., Scheper, R. J. (2000). Human natural killer T cells acquire a memory-activated phenotype before birth. Blood 95: 2440-2442 [Abstract] [Full Text]  
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• Shinkai, K., Locksley, R. M. (2000). CD1, Tuberculosis, and the Evolution of Major Histocompatibility Complex Molecules. J. Exp. Med. 191: 907-914 [Full Text]  
• Kaneko, Y., Harada, M., Kawano, T., Yamashita, M., Shibata, Y., Gejyo, F., Nakayama, T., Taniguchi, M. (2000). Augmentation of V{alpha}14 NKT Cell-mediated Cytotoxicity by Interleukin 4 in an Autocrine Mechanism Resulting in the Development of Concanavalin A-induced Hepatitis. J. Exp. Med. 191: 105-114 [Abstract] [Full Text]  
• Leite-de-Moraes, M. C., Hameg, A., Arnould, A., Machavoine, F., Koezuka, Y., Schneider, E., Herbelin, A., Dy, M. (1999). A Distinct IL-18-Induced Pathway to Fully Activate NK T Lymphocytes Independently from TCR Engagement. J. Immunol. 163: 5871-5876 [Abstract] [Full Text]  
• Housseau, F., Bright, R. K., Simonis, T., Nishimura, M. I., Topalian, S. L. (1999). Recognition of a Shared Human Prostate Cancer-Associated Antigen by Nonclassical MHC-Restricted CD8+ T Cells. J. Immunol. 163: 6330-6337 [Abstract] [Full Text]  
• Carnaud, C., Lee, D., Donnars, O., Park, S.-H., Beavis, A., Koezuka, Y., Bendelac, A. (1999). Cutting Edge: Cross-Talk Between Cells of the Innate Immune System: NKT Cells Rapidly Activate NK Cells. J. Immunol. 163: 4647-4650 [Abstract] [Full Text]  

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