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Saposins facilitate CD1d-restricted presentation of an exogenous lipid antigen to T cells

Nature Immunologyvolume 5pages175181 (2004) | Download Citation



Members of the CD1 family present antigenic lipids to T lymphocytes. CD1 molecules survey endocytic compartments for lipid antigens that are sorted into these vesicles after incorporation into the membrane bilayer, and extraction from the bilayer is likely to be a critical step for lipid association. We hypothesized that lysosomal saposins, which are cofactors required for sphingolipid degradation, might be involved in this process. Here we show that saposins, although not required for the autoreactive recognition of CD1d by natural killer T cells, are indispensable for the binding of an exogenous lipid antigen, α-galactosylceramide, to CD1d in the endocytic pathway. We suggest that saposins mobilize monomeric lipids from lysosomal membranes and facilitate their association with CD1d.

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We thank A. Ackerman, A. Chow, R. Lackman, D. Peaper, J-H Shim, R. Teel and W. Yuan for their help, and N. Dometios for manuscript preparation. Supported by the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, PO Box 208011, New Haven, 06520-8011, Connecticut, USA

    • Suk-Jo Kang
    •  & Peter Cresswell


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The authors declare no competing financial interests.

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Correspondence to Peter Cresswell.

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