Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells

Takuya Tashiro, Etsuko Sekine-Kondo, Tomokuni Shigeura, Ryusuke Nakagawa, Sayo Inoue, Miyuki Omori-Miyake, Tomoki Chiba, Naomi Hongo, Shin Ichiro Fujii, Kanako Shimizu, Yohei Yoshiga, Takayuki Sumida, Kenji Mori, Hiroshi Watarai, Masaru Taniguchi

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


NKT cells are characterized by their production of both Th1 and Th2 cytokines immediately after stimulation with α-galactosylceramide (α-GalCer), which is composed of α-galactopyranose linked to ceramide (itself composed of sphingosine and fatty-acyl chains); the chain length of the ceramide varies and this affects the ability of α-GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized α-carba-GalCer, which has an α-linked carba-galactosyl moiety; here, the 5a′-oxygen atom of the D-galactopyranose ring of α-GalCer is replaced by a methylene group. The α-carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN-γ compared with α-GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The α-carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was α-GalCer, which has an acetal bond. Modulation of the sugar moiety in glycolipids might therefore provide optimal therapeutic reagents for protective immune responses against tumor or pathogens.

Original languageEnglish
Pages (from-to)319-328
Number of pages10
JournalInternational immunology
Issue number4
Publication statusPublished - 2010 Feb 24
Externally publishedYes


  • CD1d
  • Glycolipid
  • IFN-γ
  • NKT cells
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells'. Together they form a unique fingerprint.

Cite this