Cutting edge: a naturally occurring mutation in CD1e impairs lipid antigen presentation |
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Authors: | Tourne Sylvie Maitre Blandine Collmann Anthony Layre Emilie Mariotti Sabrina Signorino-Gelo François Loch Caroline Salamero Jean Gilleron Martine Angénieux Catherine Cazenave Jean-Pierre Mori Lucia Hanau Daniel Puzo Germain De Libero Gennaro de la Salle Henri |
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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 |
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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. |
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