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* Unité 725 "Biology of Human Dendritic Cells" and
Unité 311, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France;
Etablissement Français du Sang-Alsace, Strasbourg, France;
Université Louis-Pasteur, Strasbourg, France;
¶ Experimental Immunology, Department of Research, Basel University Hospital, Basel, Switzerland;
|| Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5089, Department of Molecular Mechanisms of Mycobacterial Infections, Toulouse, France;
# Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM, Université Louis-Pasteur, Illkirch-Graffenstaden, France; and
** Imaging Center and
"Molecular Mechanisms of Intracellular Transport," UMR144 CNRS, Institut Curie, Paris, France
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, PIM6. CD1e is formed by the association of β2-microglobulin with an 
-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 PIM6 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Institut National de la Santé et de la Recherche Médicale, Etablissement Français du Sang-Alsace and Agence Nationale de Recherche Microbiologie-Maladie Emergentes (ANR-05-MIME-006), the European Union funded TB-VAC tuberculosis vaccine project (LSHP-CT-2003-503367), Swiss National Fund Grant 3100A0-109918, and the Basel Cancer League (Krebsliga Beider Basel). B.M. was the recipient of a grant from Association de Recherche et de Développement en Médecine et en Santé Publique (ARMESA).
2 Address correspondence and reprint requests to Dr. Sylvie Tourne or Dr. Henri de la Salle, Institut National de la Santé et de la Recherche Médicale, Unité 725, Etablissement Français du Sang-Alsace, 10 Rue Spielmann, 67065 Strasbourg Cedex, France. E-mail addresses: sylvie.tourne{at}efs-alsace.fr and henri.delasalle{at}efs-alsace.fr
3 Abbreviations used in this paper: ER, endoplasmic reticulum; β2m, β2-microglobulin; Endo-H, endoglycosidase H; GM1, monosialoganglioside GM1; MFI, median fluorescence intensity; PIM, phosphatidyl-myo-inositol-mannoside; PIM6, hexamannosylated phosphatidyl-myo-inositol; PNGase F, peptide N-glycosidase F; rs, recombinant soluble (prefix); WB, Western blotting.
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