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The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading

View ORCID ProfileMaria Shamin, Tomasz H. Benedyk, View ORCID ProfileStephen C. Graham, Janet E. Deane
doi: https://doi.org/10.1101/698654
Maria Shamin
1Cambridge Institute for Medical Research, University of Cambridge, Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK
2Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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Tomasz H. Benedyk
2Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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Stephen C. Graham
2Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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Janet E. Deane
1Cambridge Institute for Medical Research, University of Cambridge, Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK
3Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ
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  • For correspondence: jed55@cam.ac.uk
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Abstract

Lipid antigens are presented on the surface of cells by the CD1 family of glycoproteins, which have structural and functional similarity to MHC class I molecules. The hydrophobic lipid antigens are embedded in membranes and inaccessible to the lumenal lipid-binding domain of CD1 molecules. Therefore, CD1 molecules require lipid transfer proteins for lipid loading and editing. CD1d is loaded with lipids in late endocytic compartments, and lipid transfer proteins of the saposin family have been shown to play a crucial role in this process. However, the mechanism by which saposins facilitate lipid binding to CD1 molecules is not known and is thought to involve transient interactions between protein components to ensure CD1-lipid complexes can be efficiently trafficked to the plasma membrane for antigen presentation. Of the four saposin proteins, the importance of Saposin B (SapB) for loading of CD1d is the most well-characterised. However, a direct interaction between CD1d and SapB has yet to be described. In order to determine how SapB might load lipids onto CD1d, we used purified, recombinant CD1d and SapB and carried out a series of highly sensitive binding assays to monitor direct interactions. Using equilibrium binding analysis, chemical cross-linking and co-crystallisation experiments, under a range of different conditions, we could not demonstrate a direct interaction. This work establishes comprehensively that the role of SapB in lipid loading does not involve direct binding to CD1d. We discuss the implication of this for our understanding of lipid loading of CD1d and propose several factors that may influence this process.

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Posted July 11, 2019.
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The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading
Maria Shamin, Tomasz H. Benedyk, Stephen C. Graham, Janet E. Deane
bioRxiv 698654; doi: https://doi.org/10.1101/698654
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The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading
Maria Shamin, Tomasz H. Benedyk, Stephen C. Graham, Janet E. Deane
bioRxiv 698654; doi: https://doi.org/10.1101/698654

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