Invariant TCR rather than CD1d shapes the preferential activities of C-glycoside analogues against human versus murine invariant NKT cells

Xiangming Li, Takayuki Shiratsuchi, Guangwu Chen, Paolo Dellabona, Giulia Casorati, Richard W. Franck, Moriya Tsuji

Research output: Contribution to journalArticlepeer-review

Abstract

C-glycoside analogues of α-galactosylceramide were shown to activate both human and mouse invariant NKT (iNKT) cells. Among these analogues, GCK152, which has an aromatic ring in the acyl chain, exhibited a stronger stimulatory activity against human iNKT cells and a much weaker activity against murine iNKT cells than GCK127 that has an almost identical fatty acyl chain as α-galactosylceramide. In this study, we have found that invariant TCR (invTCR) expressed by iNKT cells, but not CD1d expressed by APCs, command the species-specific preferential activity of C-glycosides, and that their preferential activity against human vs murine iNKT cells correlate with the binding affinity of glycolipid-CD1d complex to invTCR of respective iNKT cells rather than that of glycolipid to human or murine CD1d molecules. Overall, the structural difference of invTCR appears to supersede those of CD1d molecule in shaping the strength of the biological activity of C-glycoside analogues.

Original languageEnglish
Pages (from-to)4415-4421
Number of pages7
JournalJournal of Immunology
Volume183
Issue number7
DOIs
Publication statusPublished - Oct 1 2009

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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