title: Saposins utilize two strategies for lipid transfer and CD1 antigen presentation.
abstract: Transferring lipid antigens from membranes into CD1 antigen-presenting proteins represents a major molecular hurdle necessary for T-cell recognition. Saposins facilitate this process, but the mechanisms used are not well understood. We found that saposin B forms soluble saposin protein-lipid complexes detected by native gel electrophoresis that can directly load CD1 proteins. Because saposin B must bind lipids directly to function, we found it could not accommodate long acyl chain containing lipids. In contrast, saposin C facilitates CD1 lipid loading in a different way. It uses a stable, membrane-associated topology and was capable of loading lipid antigens without forming soluble saposin-lipid antigen complexes. These findings reveal how saposins use different strategies to facilitate transfer of structurally diverse lipid antigens.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: León
authors.forename: Raju V V
authors.initials: RV
authors.lastname: Tatituri
authors.forename: Rosa
authors.initials: R
authors.lastname: Grenha
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Duarte C
authors.initials: DC
authors.lastname: Barral
authors.forename: Adriaan J
authors.initials: AJ
authors.lastname: Minnaard
authors.forename: Veemal
authors.initials: V
authors.lastname: Bhowruth
authors.forename: Natacha
authors.initials: N
authors.lastname: Veerapen
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Anne
authors.initials: A
authors.lastname: Kasmar
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004587:Electrophoresis, Agar Gel; D006017:Glycolipids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007694:Killer Cells, Natural / Q000166:cytology; D008051:Lipid Bilayers / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008954:Models, Biological; D011994:Recombinant Proteins / Q000737:chemistry; D049231:Saposins / Q000737:chemistry* / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D018949:Antigens, CD1; D006017:Glycolipids; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D011994:Recombinant Proteins; D049231:Saposins