title: Cutting edge: a naturally occurring mutation in CD1e impairs lipid antigen presentation.
abstract: The human CD1a-d proteins are plasma membrane molecules involved in the presentation of lipid Ags to T cells. In contrast, CD1e is an intracellular protein present in a soluble form in late endosomes or lysosomes and is essential for the processing of complex glycolipid Ags such as hexamannosylated phosphatidyl-myo-inositol, PIM(6). CD1e is formed by the association of beta(2)-microglobulin with an alpha-chain encoded by a polymorphic gene. We report here that one variant of CD1e with a proline at position 194, encoded by allele 4, does not assist PIM(6) presentation to CD1b-restricted specific T cells. The immunological incompetence of this CD1e variant is mainly due to inefficient assembly and poor transport of this molecule to late endosomal compartments. Although the allele 4 of CD1E is not frequent in the population, our findings suggest that homozygous individuals might display an altered immune response to complex glycolipid Ags.
authors.affiliation: Unité 725 Biology of Human Dendritic Cells, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France. sylvie.tourne@efs-alsace.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tourne
authors.forename: Blandine
authors.initials: B
authors.lastname: Maitre
authors.forename: Anthony
authors.initials: A
authors.lastname: Collmann
authors.forename: Emilie
authors.initials: E
authors.lastname: Layre
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mariotti
authors.forename: François
authors.initials: F
authors.lastname: Signorino-Gelo
authors.forename: Caroline
authors.initials: C
authors.lastname: Loch
authors.forename: Jean
authors.initials: J
authors.lastname: Salamero
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
authors.forename: Catherine
authors.initials: C
authors.lastname: Angénieux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.forename: Henri
authors.initials: H
authors.lastname: de la Salle
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics* / Q000276:immunology*; D018949:Antigens, CD1 / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D002999:Clone Cells; D011992:Endosomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005732:Gangliosides / Q000235:genetics / Q000378:metabolism; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D011499:Protein Processing, Post-Translational / Q000276:immunology; D021381:Protein Transport / Q000235:genetics / Q000276:immunology
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; C417738:CD1e antigen; D005732:Gangliosides; D006017:Glycolipids; D006023:Glycoproteins; C025447:sialogangliosides