Invariant TCR rather than CD1d shapes the preferential activities of C-glycoside analogues against human versus murine invariant NKT cells.
C-glycoside analogues of alpha-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 alpha-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.
Li
Xiangming
X
HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Shiratsuchi
Takayuki
T
Chen
Guangwu
G
Dellabona
Paolo
P
Casorati
Giulia
G
Franck
Richard W
RW
Tsuji
Moriya
M
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002240:Carbohydrate Sequence; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D005260:Female; D005699:Galactosylceramides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000276:immunology; D006027:Glycosides; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000276:immunology* / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity
D055610:Antigens, CD1d; C438934:C-glycoside; C526877:CD1D protein, human; D005699:Galactosylceramides; D006027:Glycosides; D009005:Monosaccharides; D011948:Receptors, Antigen, T-Cell; C528689:Valpha24 protein, human; C493154:alpha-galactosylceramide