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J. Exp. Med.,
Volume 188, Number 8, October 19, 1998 1529-1534
By

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 A conserved subset of mature circulating T cells in humans expresses an invariant V
Pharmaceutical Research Laboratory, Kirin Brewery, Gunma 370-12, Japan
24-J
Q T
cell receptor (TCR)-
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-
/
+ 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
-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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