CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells

Franca M. Spada, Yasuhiko Koezuka, Steven A. Porcelli

Research output: Contribution to journalArticlepeer-review

389 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1529-1534
Number of pages6
JournalJournal of Experimental Medicine
Volume188
Issue number8
DOIs
StatePublished - Oct 19 1998
Externally publishedYes

Keywords

  • Antigen presentation
  • CD1
  • Glycolipid
  • Human
  • Natural killer T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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