Sci. STKE, 10 July 2007
Structural Biology Balanced on One Foot
Nancy R. Gough
Science's STKE, AAAS, Washington, DC 20005, USA
Cd1 proteins bind lipid antigens and present them to T cells to initiate immune responses. Cd1d presents glycolipids with specific -linked sugars to the natural killer T cells (NKT) for recognition by their T cell receptor (TCR) complex. Borg et al. report the crystal structure of Cd1 bound to -galactosylceramide (-GalCer) with the NKT TCR. They find that the TCR interaction is unlike that of TCRs with the peptide-presenting major histocompatibility proteins (pMHCs). In the case of the pMHC-TCR interaction, the TCR and chains both contact the pMHC (see Moody), revealing two binding site "footprints" on the surface of the pMHC. The crystal structures reported by Borg et al. show that NKT TCR only binds to the Cd1d--GalCer by the subunit, with the subunit showing limited interaction and mostly hanging over the side of Cd1d. Moody describes the two structures as the TCR standing with both feet contacting pMHC, whereas NKT TCR appears as a pirouette balanced on one foot at the Cd1d surface. The structure also shows that the -linked galactose lies flat, optimizing the interaction surface between Cd1d and the NKT TCR, which may provide a basis for the selective recognition of -linked sugars. This study reinforces the notion that glycolipid-antigen recognition is achieved through molecular mechanisms different from those for peptide-antigen recognition and cautions against casting the Cd1 lipid-presenting proteins as MHC-like.
N. A. Borg, K. S. Wun, L. Kjer-Nielsen, M. C. J. Wilce, D. G. Pellicci, R. Koh, G. S. Besra, M. Bharadwaj, D. I. Godfrey, J. McCluskey, J. Rossjohn, CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448, 44-49 (2007). [PubMed]
D. B. Moody, How a T cell sees sugar. Nature 448, 36-37 (2007). [PubMed]
Citation: N. R. Gough, Balanced on One Foot. Sci. STKE 2007, tw244 (2007).
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