The Cellular Pathway of CD1e in Immature and Maturing Dendritic Cells

Abstract

Dendritic cells (DCs) present antigens to T cells via CD1, HLA class I or class II molecules. During maturation, HLA class II‐restricted presentation is optimized. The relocalization of CD1e from Golgi to endosomal compartments during DC maturation suggests also an optimization of the antigen‐presentation pathway via CD1 molecules. We here detail the biosynthesis and cellular pathway of CD1e in immature and maturing DCs. Unlike the other CD1 molecules, CD1e was found to reach late endosomes through sorting endosomes, without passing through the plasma membrane in either immature or maturing cells. After induction of DC maturation, CD1e disappeared rapidly from the Golgi and was transiently localized in HLA‐DR+ vesicles, while the number of CD1e+/CD1b+ compartments increased for at least 20 h. High‐resolution light microscopy showed that, in immature DCs, CD1e+ vesicles were often in close apposition to EEA1+ or HLA‐DR+ compartments, while CD1e displayed a nearly exclusive distribution in the lysosomes of mature DCs, a finding corroborated by immunoelectron microscopy. During maturation, CD1e synthesis progressively declined, while the endosomal cleavage of CD1e still occurred. Thus, CD1e displays peculiar properties, suggesting an unexpected role among the family of CD1 antigen‐presenting molecules.

Activation state and intracellular trafficking contribute to the repertoire of endogenous glycosphingolipids presented by CD1d

“…These findings may be relevant in the case of human CD1b where the lysosomal microenvironment has been shown to be important in facilitating the loading of lipids (37) and possibly, with specific endogenous GSL. In addition, CD1e has been shown to play important roles in CD1b antigen loading and to rapidly redistribute from the Golgi network to the lysosome in myeloid DC matured by LPS (38); additionally, CD1e could play a role in selecting the endogenous GSL that are bound to CD1b in both the steady state and in the setting of myeloid DC activation.…”

Fine tuning by human CD1e of lipid-specific immune responses

“…Moreover, CD1e shows a very peculiar intracellular distribution, which in dendritic cells (DCs) correlates with their maturation stage (1). In immature DCs, CD1e prevalently accumulates in the trans-Golgi network (TGN), whereas, in mature DCs, it distributes in late endosomes and lysosomes (LYs) where it is cleaved into an active soluble form (2). In LYs of mature DCs, CD1e accumulates and persists because of increased protein stability, which is associated with a progressive shortening of the carbohydrate side chains (3).…”

Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability

“…Protein concentrations were determined with the Bio-Rad Protein Assay (Bio-Rad, Munich, Germany), and cell extracts were analyzed by SDS-polyacrylamide gel electrophoresis (PAGE) on 12% polyacrylamide gels. Pulse-chase and immunoprecipitation experiments were carried out essentially as described previously (Angenieux et al, 2005). The cells were pulse labeled with [ 35 S]methionine and cysteine (Translabel) for 30 min at 150 Ci per 2 ϫ 10 6 cells in a volume of 1 ml, and then they were chased for various times in a suspension containing 4 ϫ 10 6 cells/ml in RPMI 1640 medium supplemented with 10% FCS.…”