title: Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins.
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.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhou
authors.forename: Carlos
authors.initials: C
authors.lastname: Cantu
authors.forename: Yuval
authors.initials: Y
authors.lastname: Sagiv
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schrantz
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Qi
authors.forename: Don J
authors.initials: DJ
authors.lastname: Mahuran
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Morales
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
authors.forename: Kamel
authors.initials: K
authors.lastname: Benlagha
authors.forename: Paul
authors.initials: P
authors.lastname: Savage
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d; D002352:Carrier Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D049289:G(M2) Activator Protein; D006017:Glycolipids / Q000276:immunology; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology*; D051379:Mice; D011506:Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D002352:Carrier Proteins; D049289:G(M2) Activator Protein; C511923:Gltp protein, mouse; D006017:Glycolipids; D006023:Glycoproteins; D008055:Lipids; D011506:Proteins; C483344:Psap protein, mouse; D011948:Receptors, Antigen, T-Cell; D049231:Saposins; D049128:Sphingolipid Activator Proteins; C030363:lipid transfer protein