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Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15 Å

Nature Immunology volume 4, pages 808–815 (2003)Cite this article

Abstract

CD1 antigens bind a variety of self and foreign lipid and glycolipid antigens for presentation to CD1-restricted T cell receptors (TCRs). Here we report the crystal structure of human CD1a in complex with a sulfatide self antigen at a resolution of 2.15 Å. The lipid adopts an S-shaped conformation, with the sphingosine chain completely buried in the A′ pocket and the fatty acid chain emerging from the interface of the A′ pocket into the more exposed F′ pocket. The headgroup is anchored in the A′-F′ junction and protrudes into the F′ pocket for TCR recognition. Because the A′ pocket is narrow with a fixed terminus, it can act as a molecular 'ruler' to select alkyl chains of a particular length.

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Figure 1: The human CD1a structure with a bound sulfatide antigen.
Figure 2: Conformation of the sulfatide in the CD1a binding groove.
Figure 3: 'Stereo view' of the bound lipid and headgroup conformation.
Figure 4: 'Stereo view' of CD1 and MHC class I α1-α2 binding domains.
Figure 5: Comparison of the antigen-binding grooves of CD1a, CD1b and mCD1d.

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Acknowledgements

We thank the staff of the Advanced Light Source BL 5.0.1 for support with data collection; M. Crispin, R. Stanfield, A. Heine, J. Stevens, J. Luz, N. Larsen, J. Kelly and B. Moody for discussions; X. Dai for assistance on synchrotron trips; S. Ferguson for technical assistance; R. Stefanko and M. Wallace for generating the CD1a construct; and E. Grant and M. Brenner for the CD1a cDNA. We acknowledge Syrrx for the use of their crystallization robot (initial CD1a crystallization trials). This study was supported by National Institutes of Health grants GM62116 (I.A.W.), CA58896 (I.A.W.) and AI53725 (L.T.), postdoctoral fellowships from the Deutsche Forschungsgemeinschaft and the Skaggs Institute for Chemical Biology (D.M.Z.).

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  1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Dirk M Zajonc, Marc A Elsliger & Ian A Wilson

  2. Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Luc Teyton

  3. Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Ian A Wilson

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Zajonc, D., Elsliger, M., Teyton, L. et al. Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15 Å. Nat Immunol 4, 808–815 (2003). https://doi.org/10.1038/ni948

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