The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/10/1529/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 8, October 19, 1998 1529-1534

Brief Definitive Reports

CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells

Franca M. Spada*, Yasuhiko Koezuka{ddagger}, and Steven A. Porcelli*

From the * Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and the {ddagger} Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan

A conserved subset of mature circulating T cells in humans expresses an invariant V{alpha}24-J{alpha}Q T cell receptor (TCR)-{alpha} chain rearrangement and several natural killer (NK) locus–encoded C-type lectins. These human T cells appear to be precise homologues of the subset of NK1.1+ TCR-{alpha}/β+ T cells, often referred to as NK T cells, which was initially identified in mice. Here we show that human NK T cell clones are strongly and specifically activated by the same synthetic glycolipid antigens as have been shown recently to stimulate murine NK T cells. Responses of human NK T cells to these synthetic glycolipids, consisting of certain {alpha}-anomeric sugars conjugated to an acylated phytosphingosine base, required presentation by antigen-presenting cells expressing the major histocompatibility complex class I–like CD1d protein. Presentation of synthetic glycolipid antigens to human NK T cells required internalization of the glycolipids by the antigen-presenting cell and normal endosomal targeting of CD1d. Recognition of these compounds by human NK T cells triggered proliferation, cytokine release, and cytotoxic activity. These results demonstrate a striking parallel in the specificity of NK T cells in humans and mice, thus providing further insight into the potential mechanisms of immune recognition by NK T cells and the immunological function of this unique T cell subset.

Key Words: natural killer T cell • human • CD1 • antigen presentation • glycolipid

Address correspondence to Steven A. Porcelli, Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Rm. 516B Smith Bldg., 1 Jimmy Fund Way, Boston, MA 02115. Phone: 617-525-1031; Fax: 617-525-1010; E-mail: sporcelli{at}rics.bwh.harvard.edu


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