A conserved subset of mature circulating T cells in humans expresses an invariant Vα24-JαQ T cell receptor (TCR)-α 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-α/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 α-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.
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19 October 1998
Brief Definitive Report|
October 19 1998
CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells
Franca M. Spada,
Franca M. Spada
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 ‡Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
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Yasuhiko Koezuka,
Yasuhiko Koezuka
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 ‡Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
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Steven A. Porcelli
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 ‡Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
Search for other works by this author on:
Franca M. Spada
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 ‡Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
Yasuhiko Koezuka
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 ‡Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
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 ‡Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
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: [email protected]
Received:
June 16 1998
Revision Received:
July 20 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (8): 1529–1534.
Article history
Received:
June 16 1998
Revision Received:
July 20 1998
Citation
Franca M. Spada, Yasuhiko Koezuka, Steven A. Porcelli; CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells . J Exp Med 19 October 1998; 188 (8): 1529–1534. doi: https://doi.org/10.1084/jem.188.8.1529
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