title: Functional CD1a is stabilized by exogenous lipids.
abstract: Self-glycosphingolipids bind to surface CD1 molecules and are readily displaced by other CD1 ligands. This capacity to exchange antigens at the cell surface is not common to other antigen-presenting molecules and its physiological importance is unclear. Here we show that a large pool of cell-surface CD1a, but not CD1b molecules, is stabilized by exogenous lipids present in serum. Under serum deprivation CD1a molecules are altered and functionally inactive, as they are unable to present lipid antigens to T cells. Glycosphingolipids and phospholipids bind to, and restore functionality to CD1a without the contribution of newly synthesized and recycling CD1a molecules. The dependence of CD1a stability on exogenous lipids is not related to its intracellular traffic and rather to its antigen-binding pockets. These results indicate a functional dichotomy between CD1a and CD1b molecules and provide new information on how the lipid antigenic repertoire is immunologically sampled.
authors.affiliation: Experimental Immunology, Department of Research University Hospital, Basel, Switzerland.
authors.forename: Vania
authors.initials: V
authors.lastname: Manolova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kistowska
authors.forename: Samantha
authors.initials: S
authors.lastname: Paoletti
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Baltariu
authors.forename: Huguette
authors.initials: H
authors.lastname: Bausinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
mesh_terms: D018949:Antigens, CD1 / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006028:Glycosphingolipids / Q000494:pharmacology; D006801:Humans; D007801:Langerhans Cells / Q000737:chemistry; D008055:Lipids / Q000494:pharmacology*; D018613:Microscopy, Confocal; D010743:Phospholipids / Q000494:pharmacology; D017510:Protein Folding; D044967:Serum / Q000502:physiology; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000494:pharmacology
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D006028:Glycosphingolipids; D008055:Lipids; D010743:Phospholipids; D013433:Sulfoglycosphingolipids; D001613:beta 2-Microglobulin