Abstract
It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Valpha14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the loading as well as the editing of lipids on CD1. Transient complexes between CD1, lipid, and LTP suggested a "tug-of-war" model in which lipid exchange between CD1 and LTP is on the basis of their respective affinities for lipids. LTPs constitute a previously unknown link between lipid metabolism and immunity and are likely to exert a profound influence on the repertoire of self, tumor, and microbial lipid antigens.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen Presentation*
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, CD1 / immunology*
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Antigens, CD1 / metabolism
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Antigens, CD1d
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Carrier Proteins / metabolism*
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Endosomes / metabolism*
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G(M2) Activator Protein
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Glycolipids / immunology
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Glycoproteins / deficiency
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Glycoproteins / genetics
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Glycoproteins / metabolism
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Glycoproteins / physiology*
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Killer Cells, Natural / immunology
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Lipid Metabolism
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Lipids / immunology*
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Mice
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Proteins / metabolism
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Receptors, Antigen, T-Cell / immunology
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Saposins
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Sphingolipid Activator Proteins
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T-Lymphocytes / immunology*
Substances
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Antigens, CD1
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Antigens, CD1d
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Carrier Proteins
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G(M2) Activator Protein
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Gltp protein, mouse
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Glycolipids
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Glycoproteins
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Lipids
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Proteins
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Psap protein, mouse
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Receptors, Antigen, T-Cell
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Saposins
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Sphingolipid Activator Proteins
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lipid transfer protein