Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers

Jennifer L. Matsuda, Olga V. Naidenko, Laurent Gapin, Toshinori Nakayama, Masaru Taniguchi, Chyung Ru Wang, Yasuhiko Koezuka, Mitchell Kronenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

773 Scopus citations


A major group of natural killer (NK) T cells express an invariant Vα14+ T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14+ NK T cells. Using these tetramers, we find that α-GalCer-specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1- but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of α-GalCer leads to the production of both interferon γ and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that α-GalCer-specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.

Original languageEnglish (US)
Pages (from-to)741-753
Number of pages13
JournalJournal of Experimental Medicine
Issue number5
StatePublished - Sep 4 2000


  • Antigen presentation
  • Lipid antigen
  • Natural killer cell
  • T lymphocyte
  • Tetramer

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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