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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901021v1 183/7/4415    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Li, X. Articles by Tsuji, M. PubMed PubMed Citation Articles by Li, X. Articles by Tsuji, M.

Invariant TCR Rather Than CD1d Shapes the Preferential Activities of C-Glycoside Analogues Against Human Versus Murine Invariant NKT Cells¹

Xiangming Li^*, Takayuki Shiratsuchi^*, Guangwu Chen, Paolo Dellabona, Giulia Casorati, Richard W. Franck and Moriya Tsuji^2,*

^* HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016; Department of Chemistry, Hunter College of the City University of New York, New York, NY 10021; and Experimental Immunology Unit, Department of Immunology, Transplantation and Infectious Disease, DIBIT, H. San Raffaele Scientific Institute, Milano, Italy

C-glycoside analogues of -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 -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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by National Institutes of Health Grants R21 AI062842 and R56 AI070258 (to M.T.), Cytheris, Otsuka Pharmaceutical Company, the Irene Diamond Foundation, Bill and Melinda Gates Foundation, a subcontract from N01-AI-25456-MODno.5 (to R.W.F.), and Italian Association for Cancer Research and Italian Ministry of Health (to G.C. and P.D.).

² Address correspondence and reprint requests to Dr. M. Tsuji, HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016. E-mail address: mtsuji{at}adarc.org

³ Abbreviations used in this paper: iNKT, invariant NKT cell; invTCR, invariant T cell receptor; -GalCer, -galactosylceramide; DC, dendritic cell.