CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells.
A conserved subset of mature circulating T cells in humans expresses an invariant Valpha24-JalphaQ 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/beta+ 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.
Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
F M
FM
Spada
Y
Y
Koezuka
S A
SA
Porcelli
D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000502:physiology*; D006017:Glycolipids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice
D018949:Antigens, CD1; D006017:Glycolipids